Disease Information

General Information of the Disease (ID: DIS00006)

• Name: Solid tumour/cancer
• ICD: ICD-11: 2A00-2F9Z

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 41 drug(s) in total

Avapritinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Drug: Avapritinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: M230 cells; Skin; Homo sapiens (Human); CVCL_D749
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Drug: Avapritinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: M-07e cells; Peripheral blood; Homo sapiens (Human); CVCL_2106
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: Chinese hamster ovary (CHO)-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay; Cellular proliferation test assay

Axitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V559D (c.1676T>A)
• Sensitive Drug: Axitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V559A (c.1676T>C)
• Sensitive Drug: Axitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V559G (c.1676T>G)
• Sensitive Drug: Axitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L576P (c.1727T>C)
• Sensitive Drug: Axitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V654A (c.1961T>C)
• Sensitive Drug: Axitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T670I (c.2009C>T)
• Sensitive Drug: Axitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [3]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.A829P (c.2485G>C)
• Sensitive Drug: Axitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: GIST-T1 cells; Gastric; Homo sapiens (Human); CVCL_4976
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST-5R cells; Gastric; Homo sapiens (Human); CVCL_A9M9
• In Vitro Model: GIST-48B cells; Gastric; Homo sapiens (Human); CVCL_M441
• In Vivo Model: Female BALB/c-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome shotgun sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Tyrosine-protein kinase ABL1 (ABL1) [4]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T315I (c.944C>T)
• Sensitive Drug: Axitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; .
• Mechanism Description: The missense mutation p.T315I (c.944C>T) in gene ABL1 cause the sensitivity of Axitinib by aberration of the drug's therapeutic target

Binimetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [5]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Drug: Binimetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: Phoenix AMPHO cells; Fetal kidney; Homo sapiens (Human); CVCL_H716
• In Vivo Model: NOD scid gamma xenograft model; Mus musculus
• Experiment for Molecule Alteration: Single cell sequencing assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [6]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q61R (c.182A>G)
• Sensitive Drug: Binimetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: RL952 cells; Endometrium; Homo sapiens (Human); CVCL_0505
• In Vitro Model: NCI-H1915 cells; Lung; Homo sapiens (Human); CVCL_1505
• In Vitro Model: KYSE-30 cells; Esophagus; Homo sapiens (Human); CVCL_1351
• In Vitro Model: KNS62 cells; Brain; Homo sapiens (Human); CVCL_1335
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: HCC44 cells; Lung; Homo sapiens (Human); CVCL_2060
• In Vitro Model: CAL-12T cells; Lung; Homo sapiens (Human); CVCL_1105
• In Vivo Model: CB17 SCID-/- mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Key Molecule: GTPase Hras (HRAS) [6]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G12V (c.35G>T)
• Sensitive Drug: Binimetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: RL952 cells; Endometrium; Homo sapiens (Human); CVCL_0505
• In Vitro Model: NCI-H1915 cells; Lung; Homo sapiens (Human); CVCL_1505
• In Vitro Model: KYSE-30 cells; Esophagus; Homo sapiens (Human); CVCL_1351
• In Vitro Model: KNS62 cells; Brain; Homo sapiens (Human); CVCL_1335
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: HCC44 cells; Lung; Homo sapiens (Human); CVCL_2060
• In Vitro Model: CAL-12T cells; Lung; Homo sapiens (Human); CVCL_1105
• In Vivo Model: CB17 SCID-/- mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Brigatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: ALK tyrosine kinase receptor (ALK) [7]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G1202R (c.3604G>A)
• Resistant Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Thymidine Incorporation assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: ALK tyrosine kinase receptor (ALK) [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G1128A (c.3383G>C)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: CLB-GE cells; Bone marrow; Homo sapiens (Human); CVCL_9530
• In Vitro Model: CLB-BAR cells; Brain; Homo sapiens (Human); CVCL_9519
• In Vivo Model: Female Balbc/nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.G1128A (c.3383G>C) in gene ALK cause the sensitivity of Brigatinib by aberration of the drug's therapeutic target

Key Molecule: ALK tyrosine kinase receptor (ALK) [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I1171N (c.3512T>A)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: CLB-GE cells; Bone marrow; Homo sapiens (Human); CVCL_9530
• In Vitro Model: CLB-BAR cells; Brain; Homo sapiens (Human); CVCL_9519
• In Vivo Model: Female Balbc/nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.I1171N (c.3512T>A) in gene ALK cause the sensitivity of Brigatinib by aberration of the drug's therapeutic target

Key Molecule: ALK tyrosine kinase receptor (ALK) [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F1174L (c.3520T>C)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: CLB-GE cells; Bone marrow; Homo sapiens (Human); CVCL_9530
• In Vitro Model: CLB-BAR cells; Brain; Homo sapiens (Human); CVCL_9519
• In Vivo Model: Female Balbc/nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.F1174L (c.3520T>C) in gene ALK cause the sensitivity of Brigatinib by aberration of the drug's therapeutic target

Key Molecule: ALK tyrosine kinase receptor (ALK) [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R1192P (c.3575G>C)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: CLB-GE cells; Bone marrow; Homo sapiens (Human); CVCL_9530
• In Vitro Model: CLB-BAR cells; Brain; Homo sapiens (Human); CVCL_9519
• In Vivo Model: Female Balbc/nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.R1192P (c.3575G>C) in gene ALK cause the sensitivity of Brigatinib by aberration of the drug's therapeutic target

Key Molecule: ALK tyrosine kinase receptor (ALK) [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F1245C (c.3734T>G)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: CLB-GE cells; Bone marrow; Homo sapiens (Human); CVCL_9530
• In Vitro Model: CLB-BAR cells; Brain; Homo sapiens (Human); CVCL_9519
• In Vivo Model: Female Balbc/nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.F1245C (c.3734T>G) in gene ALK cause the sensitivity of Brigatinib by aberration of the drug's therapeutic target

Key Molecule: ALK tyrosine kinase receptor (ALK) [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R1275Q (c.3824G>A)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: CLB-GE cells; Bone marrow; Homo sapiens (Human); CVCL_9530
• In Vitro Model: CLB-BAR cells; Brain; Homo sapiens (Human); CVCL_9519
• In Vivo Model: Female Balbc/nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.R1275Q (c.3824G>A) in gene ALK cause the sensitivity of Brigatinib by aberration of the drug's therapeutic target

Key Molecule: ALK tyrosine kinase receptor (ALK) [8]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1278S (c.3833A>C)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: CLB-GE cells; Bone marrow; Homo sapiens (Human); CVCL_9530
• In Vitro Model: CLB-BAR cells; Brain; Homo sapiens (Human); CVCL_9519
• In Vivo Model: Female Balbc/nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.Y1278S (c.3833A>C) in gene ALK cause the sensitivity of Brigatinib by aberration of the drug's therapeutic target

Key Molecule: ALK tyrosine kinase receptor (ALK) [7]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G1269A (c.3806G>C)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: PC12 cells; Adrenal gland; Rattus norvegicus (Rat); CVCL_0481
• In Vitro Model: CLB-PE cells; Brain; Homo sapiens (Human); CVCL_9534
• In Vitro Model: CLB-GE cells; Bone marrow; Homo sapiens (Human); CVCL_9530
• In Vitro Model: CLB-BAR cells; Brain; Homo sapiens (Human); CVCL_9519
• In Vivo Model: Female Balbc/nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Resazurin assay

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [9]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.E746_A750delELREA (c.2236_2250del15)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: U937 cells; Blood; Homo sapiens (Human); CVCL_0007
• In Vitro Model: H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vitro Model: SU-DHL-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_0538
• In Vitro Model: L-82 cells; Pleural effusion; Homo sapiens (Human); CVCL_2098
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: H838 cells; Lymph node; Homo sapiens (Human); CVCL_1594
• In Vitro Model: H-4-II-E cells; Liver; Rattus norvegicus (Rat); CVCL_0284
• In Vitro Model: H358 cells; Lung; Homo sapiens (Human); CVCL_1559
• In Vitro Model: H2228 cells; Lung; Homo sapiens (Human); CVCL_1543
• In Vitro Model: DEL cells; Pleural effusion; Homo sapiens (Human); CVCL_1170
• In Vivo Model: SCID beige mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Non-small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain. Mutations that confer resistance to second-generation ALK TKIs ceritinib and alectinib have also been identified. Brigatinib is the only TKI to maintain substantial activity against the most recalcitrant ALK resistance mutation, G1202R. The unique, potent, and pan-ALK mutant activity of brigatinib could be rationalized by structural analyses.

Key Molecule: Epidermal growth factor receptor (EGFR) [9]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: Brigatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: U937 cells; Blood; Homo sapiens (Human); CVCL_0007
• In Vitro Model: H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SUP-M2 cells; Colon; Homo sapiens (Human); CVCL_2209
• In Vitro Model: KARPAS-299 cells; Peripheral blood; Homo sapiens (Human); CVCL_1324
• In Vitro Model: SU-DHL-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_0538
• In Vitro Model: L-82 cells; Pleural effusion; Homo sapiens (Human); CVCL_2098
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: H838 cells; Lymph node; Homo sapiens (Human); CVCL_1594
• In Vitro Model: H-4-II-E cells; Liver; Rattus norvegicus (Rat); CVCL_0284
• In Vitro Model: H358 cells; Lung; Homo sapiens (Human); CVCL_1559
• In Vitro Model: H2228 cells; Lung; Homo sapiens (Human); CVCL_1543
• In Vitro Model: DEL cells; Pleural effusion; Homo sapiens (Human); CVCL_1170
• In Vivo Model: SCID beige mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Non-small cell lung cancers (NSCLCs) harboring ALK gene rearrangements (ALK+) typically become resistant to the first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) crizotinib through development of secondary resistance mutations in ALK or disease progression in the brain. Mutations that confer resistance to second-generation ALK TKIs ceritinib and alectinib have also been identified. Brigatinib is the only TKI to maintain substantial activity against the most recalcitrant ALK resistance mutation, G1202R. The unique, potent, and pan-ALK mutant activity of brigatinib could be rationalized by structural analyses.

Cabozantinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Resistant Drug: Cabozantinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 32D cells; Bone marrow; Homo sapiens (Human); CVCL_0118
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.D816V (c.2447A>T) in gene KIT cause the resistance of Cabozantinib by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1003F (c.3008A>T)
• Sensitive Drug: Cabozantinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1010Y (c.3028G>T)
• Sensitive Drug: Cabozantinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Hepatocyte growth factor receptor (MET) [12]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228N (c.3682G>A)
• Sensitive Drug: Cabozantinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Athymic female mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MET mutations Y1248H and D1246N are resistance mechanisms for type I MET-TKIs. NIH3T3 cells expressing either mutation showed resistance to both INC280 and crizotinib but not cabozantinib, indicating the potential of sequential use of MET inhibitors may lead to a more durable response.

Key Molecule: Hepatocyte growth factor receptor (MET) [13]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228V (c.3683A>T)
• Sensitive Drug: Cabozantinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: There is a patient with metastatic NSCLC with MET-mediated resistance to EGFR TKI who responded to treatment with a type I MET inhibitor, savolitinib, given in combination with a third-generation EGFR inhibitor, osimertinib. The patient then developed acquired resistance mediated by a novel MET kinase domain mutation.

Key Molecule: Hepatocyte growth factor receptor (MET) [12]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230H (c.3688T>C)
• Sensitive Drug: Cabozantinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Athymic female mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MET mutations Y1248H and D1246N are resistance mechanisms for type I MET-TKIs. NIH3T3 cells expressing either mutation showed resistance to both INC280 and crizotinib but not cabozantinib, indicating the potential of sequential use of MET inhibitors may lead to a more durable response.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase ABL1 (ABL1) [14]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V299L (c.895G>C)
• Sensitive Drug: Cabozantinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ph+ALL cells; N.A.; .; N.A.
• Mechanism Description: The missense mutation p.V299L (c.895G>C) in gene ABL1 cause the sensitivity of Cabozantinib by aberration of the drug's therapeutic target

Capmatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Hepatocyte growth factor receptor (MET) [12]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230H (c.3688T>C)
• Resistant Drug: Capmatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Athymic female mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MET mutations Y1248H and D1246N are resistance mechanisms for type I MET-TKIs. NIH3T3 cells expressing either mutation showed resistance to both INC280 and crizotinib but not cabozantinib, indicating the potential of sequential use of MET inhibitors may lead to a more durable response.

Key Molecule: Hepatocyte growth factor receptor (MET) [12]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228N (c.3682G>A)
• Resistant Drug: Capmatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Athymic female mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MET mutations Y1248H and D1246N are resistance mechanisms for type I MET-TKIs. NIH3T3 cells expressing either mutation showed resistance to both INC280 and crizotinib but not cabozantinib, indicating the potential of sequential use of MET inhibitors may lead to a more durable response.

Key Molecule: Hepatocyte growth factor receptor (MET) [13]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228V (c.3683A>T)
• Resistant Drug: Capmatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: There is a patient with metastatic NSCLC with MET-mediated resistance to EGFR TKI who responded to treatment with a type I MET inhibitor, savolitinib, given in combination with a third-generation EGFR inhibitor, osimertinib. The patient then developed acquired resistance mediated by a novel MET kinase domain mutation.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1003F (c.3008A>T)
• Sensitive Drug: Capmatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1010Y (c.3028G>T)
• Sensitive Drug: Capmatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Carboplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: TP53 target 1 (TP53TG1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Carboplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Carboplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: TP53 target 1 (TP53TG1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Conivaptan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Heme oxygenase 1 (HMOX1) [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Function; Inhibition
• Resistant Drug: Conivaptan
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ATCC 293T cells; Fetal kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Resazurin assay
• Mechanism Description: HMOX1, PRKCA, and NEIL2 contribute to anthracycline resistance within the more complex MDR phenotype, while P-glycoprotein/ABCB1 overexpression causes not only anthracycline resistance but also resistance to other anticancer drug classes. Conivaptan has the potential to be used as the dual inhibitor of HMOX1 and PRKCA, whereas bexarotene has the potential as an HMOX1 inhibitor and desloratadine as a PRKCA inhibitor.

Key Molecule: Protein kinase C alpha (PRKCA) [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Function; Inhibition
• Resistant Drug: Conivaptan
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ATCC 293T cells; Fetal kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Resazurin assay
• Mechanism Description: HMOX1, PRKCA, and NEIL2 contribute to anthracycline resistance within the more complex MDR phenotype, while P-glycoprotein/ABCB1 overexpression causes not only anthracycline resistance but also resistance to other anticancer drug classes. Conivaptan has the potential to be used as the dual inhibitor of HMOX1 and PRKCA, whereas bexarotene has the potential as an HMOX1 inhibitor and desloratadine as a PRKCA inhibitor.

Dacomitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [17]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.Y764_V765insHH (c.2292_2293insCATCAT)
• Resistant Drug: Dacomitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Epidermal growth factor receptor (EGFR) [17]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.A767_V769 (c.2299_2307)
• Resistant Drug: Dacomitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Epidermal growth factor receptor (EGFR) [17]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Resistant Drug: Dacomitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• Resistant Drug: Dacomitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [17]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.D770_770delinsGY (c.2308_2310delinsGGTTAT)
• Sensitive Drug: Dacomitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [17]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.M774_774delinsWLV (c.2320_2322delinsTGGCTTGTA)
• Sensitive Drug: Dacomitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [17]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)
• Sensitive Drug: Dacomitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [17]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.G778_S779insCPG (c.2335_2336insGTCCTGGTT)
• Sensitive Drug: Dacomitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Epidermal growth factor receptor (EGFR) [19]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E709K (c.2125G>A)
• Sensitive Drug: Dacomitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: myelomonocyti cells; Bone marrow; Homo sapiens (Human); N.A.
• In Vitro Model: macrophage-like cells; N.A.; .; N.A.
• In Vitro Model: IL3-dependent murine pro-B cells; Blood; Homo sapiens (Human); N.A.
• In Vitro Model: Balb/C mouse leukemia cells; Blood; Mus musculus (Mouse); CVCL_9099
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Epidermal growth factor receptor (EGFR) [19]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.E709_T710delinsD (c.2127_2129delAAC)
• Sensitive Drug: Dacomitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: myelomonocyti cells; Bone marrow; Homo sapiens (Human); N.A.
• In Vitro Model: macrophage-like cells; N.A.; .; N.A.
• In Vitro Model: IL3-dependent murine pro-B cells; Blood; Homo sapiens (Human); N.A.
• In Vitro Model: Balb/C mouse leukemia cells; Blood; Mus musculus (Mouse); CVCL_9099
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Epidermal growth factor receptor (EGFR) [19]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G719A (c.2156G>C)
• Sensitive Drug: Dacomitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: myelomonocyti cells; Bone marrow; Homo sapiens (Human); N.A.
• In Vitro Model: macrophage-like cells; N.A.; .; N.A.
• In Vitro Model: IL3-dependent murine pro-B cells; Blood; Homo sapiens (Human); N.A.
• In Vitro Model: Balb/C mouse leukemia cells; Blood; Mus musculus (Mouse); CVCL_9099
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: Dacomitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• Sensitive Drug: Dacomitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Daunorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [20]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Daunorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CR1R12 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: NIH-G185 cells; Ovary; Homo sapiens (Human); CVCL_L991
• Experiment for Drug Resistance: propidium iodide staining assay
• Mechanism Description: In a NIH-G185 cell line presenting an overexpressed amount of the human transporter P-gp, cholesterol caused dramatic inhibition of daunorubicin transport with an IC(50) of about 8 microM yet had no effect on the parent cell line nor rhodamine 123 transport.

Desloratadine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein kinase C alpha (PRKCA) [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Function; Inhibition
• Resistant Drug: Desloratadine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ATCC 293T cells; Fetal kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Resazurin assay
• Mechanism Description: HMOX1, PRKCA, and NEIL2 contribute to anthracycline resistance within the more complex MDR phenotype, while P-glycoprotein/ABCB1 overexpression causes not only anthracycline resistance but also resistance to other anticancer drug classes. Conivaptan has the potential to be used as the dual inhibitor of HMOX1 and PRKCA, whereas bexarotene has the potential as an HMOX1 inhibitor and desloratadine as a PRKCA inhibitor.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: TP53 target 1 (TP53TG1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-495 [21]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780C cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780DX5 cells; Ovary; Homo sapiens (Human); CVCL_4T98
• In Vitro Model: SGC7901R cells; Uterus; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Annexin-V-FITC apoptosis detection assay; Caspase-3 activity assay; MTT assay; Trypan blue exclusion assay
• Mechanism Description: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression, miR-495 was predicted to target ABCB1, which encodes protein MDR1.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [21]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780C cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780DX5 cells; Ovary; Homo sapiens (Human); CVCL_4T98
• In Vitro Model: SGC7901R cells; Uterus; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Annexin-V-FITC apoptosis detection assay; Caspase-3 activity assay; MTT assay; Trypan blue exclusion assay
• Mechanism Description: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression, miR-495 was predicted to target ABCB1, which encodes protein MDR1.

Erdafitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [22]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Sensitive Drug: Erdafitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [22]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Sensitive Drug: Erdafitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Erlotinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
• Resistant Drug: Erlotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Resistant Drug: Erlotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• Resistant Drug: Erlotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Infigratinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V564F (c.1690G>T)
• Resistant Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V564F (c.1690G>T) in gene FGFR2 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Resistant Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Resistant Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V555L (c.1663G>C)
• Resistant Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555L (c.1663G>C) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Resistant Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Resistant Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Sensitive Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Sensitive Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Sensitive Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Sensitive Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.R248C (c.742C>T) in gene FGFR3 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Sensitive Drug: Infigratinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of Infigratinib by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [25]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.S267_D273 (c.799_819)
• Sensitive Drug: Infigratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [25]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.W290_I291delinsC (c.870_872delGAT)
• Sensitive Drug: Infigratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay

Irinotecan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: TP53 target 1 (TP53TG1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Irinotecan
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Irinotecan
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Lapatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
• Resistant Drug: Lapatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Resistant Drug: Lapatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• Resistant Drug: Lapatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Larotrectinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tropomyosin-related kinase A (TrkA) [26]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G595R (c.1783G>A)
• Resistant Drug: Larotrectinib
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: NT-3 growth factor receptor (TrkC) [26]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G623R (c.1867G>A)
• Resistant Drug: Larotrectinib
• Experimental Note: Identified from the Human Clinical Data

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: NT-3 growth factor receptor (TrkC) [27]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Other; .
• Sensitive Drug: Larotrectinib
• Experimental Note: Identified from the Human Clinical Data

Lenvatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Sensitive Drug: Lenvatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Lenvatinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Sensitive Drug: Lenvatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Lenvatinib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Sensitive Drug: Lenvatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Lenvatinib by aberration of the drug's therapeutic target

Midostaurin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [28]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.S451F (c.1352C>T)
• Resistant Drug: Midostaurin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.S451F (c.1352C>T) in gene FLT3 cause the resistance of Midostaurin by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [29]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Drug: Midostaurin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [30]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.I836delI (c.2508_2510delCAT)
• Sensitive Drug: Midostaurin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The if-deletion p.I836delI (c.2508_2510delCAT) in gene FLT3 cause the sensitivity of Midostaurin by aberration of the drug's therapeutic target.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Drug: Midostaurin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: M230 cells; Skin; Homo sapiens (Human); CVCL_D749
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [28]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y572C (c.1715A>G)
• Sensitive Drug: Midostaurin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.Y572C (c.1715A>G) in gene FLT3 cause the sensitivity of Midostaurin by unusual activation of pro-survival pathway

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [28]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V592G (c.1775T>G)
• Sensitive Drug: Midostaurin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.V592G (c.1775T>G) in gene FLT3 cause the sensitivity of Midostaurin by unusual activation of pro-survival pathway

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [28]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R834Q (c.2501G>A)
• Sensitive Drug: Midostaurin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.R834Q (c.2501G>A) in gene FLT3 cause the sensitivity of Midostaurin by unusual activation of pro-survival pathway

Mitoxantrone

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [31]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C592A
• Sensitive Drug: Mitoxantrone
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cytotoxicity assay
• Mechanism Description: Cys-603 alone displayed mitoxantrone resistance close (although not identical) to the wt (-70%), whereas both Cys-608 alone and Cys-592 alone displayed an almost identical low resistance of -10 and 5% of the wt, respectively. For both C603A/C608A and C592A/C603A, we observed a marked decrease in resistance to mitoxantrone and a concomitant decrease in expr.

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [31]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C592A+p.C603A
• Sensitive Drug: Mitoxantrone
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cytotoxicity assay
• Mechanism Description: Cys-603 alone displayed mitoxantrone resistance close (although not identical) to the wt (-70%), whereas both Cys-608 alone and Cys-592 alone displayed an almost identical low resistance of -10 and 5% of the wt, respectively. For both C603A/C608A and C592A/C603A, we observed a marked decrease in resistance to mitoxantrone and a concomitant decrease in expr.

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [31]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C603A+p.C608A
• Sensitive Drug: Mitoxantrone
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cytotoxicity assay
• Mechanism Description: Cys-603 alone displayed mitoxantrone resistance close (although not identical) to the wt (-70%), whereas both Cys-608 alone and Cys-592 alone displayed an almost identical low resistance of -10 and 5% of the wt, respectively. For both C603A/C608A and C592A/C603A, we observed a marked decrease in resistance to mitoxantrone and a concomitant decrease in expr.

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [31]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C608A
• Sensitive Drug: Mitoxantrone
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cytotoxicity assay
• Mechanism Description: Cys-603 alone displayed mitoxantrone resistance close (although not identical) to the wt (-70%), whereas both Cys-608 alone and Cys-592 alone displayed an almost identical low resistance of -10 and 5% of the wt, respectively. For both C603A/C608A and C592A/C603A, we observed a marked decrease in resistance to mitoxantrone and a concomitant decrease in expr.

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [32]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K86M
• Sensitive Drug: Mitoxantrone
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colorimetric cytotoxicity assy assay
• Mechanism Description: Cells expressing ABCG2-wt or ABCG2-wt-MYC showed increased resistance to mitoxantrone as reflected in a sevenfold increase in IC50 value as compared to that observed for non-transfected cells (0.36 uM and 0.29 uM, for ABCG2-wt or ABCG2-wt-MYC expressing cells compared to 0.05 uM in non-transfected cells). ABCG2-k86M and ABCG2-k86M-HA displayed sensitivity comparable to that of non-transfected cells consistent with loss of function with IC50 values for mitoxantrone of 0.047 uM and and 0.043 uM

Neratinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• Resistant Drug: Neratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
• Sensitive Drug: Neratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: Neratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Osimertinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
• Resistant Drug: Osimertinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• Resistant Drug: Osimertinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: Osimertinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: TP53 target 1 (TP53TG1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [15]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Oxaliplatin
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p53 signaling pathway; Inhibition; hsa04115
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: GCIY cells; Gastric; Homo sapiens (Human); CVCL_1228
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: MkN-7 cells; Gastric; Homo sapiens (Human); CVCL_1417
• In Vitro Model: SNU-1 cells; Gastric; Homo sapiens (Human); CVCL_0099
• In Vitro Model: TGBC11TkB cells; Gastric; Homo sapiens (Human); CVCL_1768
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; TUNEL assay; xCELLigence Real-Time invasion and migration assays
• Mechanism Description: TP53TG1, a p53-induced LncRNA, binds to the multifaceted RNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. The epigenetic silencing of TP53TG1 in cancer cells promotes the YBX1-mediated activation of the PI3k/AkT pathway, which then creates further resistance not only to common chemotherapy RNA-damaging agents but also to small drug-targeted inhibitors.

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-495 [21]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780C cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780DX5 cells; Ovary; Homo sapiens (Human); CVCL_4T98
• In Vitro Model: SGC7901R cells; Uterus; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Annexin-V-FITC apoptosis detection assay; Caspase-3 activity assay; MTT assay; Trypan blue exclusion assay
• Mechanism Description: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression, miR-495 was predicted to target ABCB1, which encodes protein MDR1.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [21]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Paclitaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780C cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780DX5 cells; Ovary; Homo sapiens (Human); CVCL_4T98
• In Vitro Model: SGC7901R cells; Uterus; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Annexin-V-FITC apoptosis detection assay; Caspase-3 activity assay; MTT assay; Trypan blue exclusion assay
• Mechanism Description: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression, miR-495 was predicted to target ABCB1, which encodes protein MDR1.

Pexidartinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [33]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D835Y (c.2503G>T)
• Resistant Drug: Pexidartinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vivo Model: (Nu/Nu) male MV4; 11 xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; ATPlite 1step luminescence assay

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [33]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D835V (c.2504A>T)
• Resistant Drug: Pexidartinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vivo Model: (Nu/Nu) male MV4; 11 xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; ATPlite 1step luminescence assay

Regorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [29]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [29]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [34]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.P551_E554delPMYE (c.1651_1662del12)
• Resistant Drug: Regorafenib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-derived cells; N.A.; .; N.A.
• In Vivo Model: Female CB.17/SCID mouse xenograft model; female NOD/SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallography assay
• Experiment for Drug Resistance: CellTiter-96 AQueous One assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [34]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816H (c.2446G>C)
• Resistant Drug: Regorafenib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-derived cells; N.A.; .; N.A.
• In Vivo Model: Female CB.17/SCID mouse xenograft model; female NOD/SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallography assay
• Experiment for Drug Resistance: CellTiter-96 AQueous One assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Drug: Regorafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [34]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.P551_K558delPMYEVQWK (c.1650_1673del24)
• Sensitive Drug: Regorafenib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-derived cells; N.A.; .; N.A.
• In Vivo Model: Female CB.17/SCID mouse xenograft model; female NOD/SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallography assay
• Experiment for Drug Resistance: CellTiter-96 AQueous One assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [34]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.W557_K558delWK (c.1669_1674delTGGAAG)
• Sensitive Drug: Regorafenib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-derived cells; N.A.; .; N.A.
• In Vivo Model: Female CB.17/SCID mouse xenograft model; female NOD/SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallography assay
• Experiment for Drug Resistance: CellTiter-96 AQueous One assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [34]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.K558_558delinsNP (c.1672_1674delinsAACCCT)
• Sensitive Drug: Regorafenib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-derived cells; N.A.; .; N.A.
• In Vivo Model: Female CB.17/SCID mouse xenograft model; female NOD/SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallography assay
• Experiment for Drug Resistance: CellTiter-96 AQueous One assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [34]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V560D (c.1679T>A)
• Sensitive Drug: Regorafenib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: GIST-derived cells; N.A.; .; N.A.
• In Vivo Model: Female CB.17/SCID mouse xenograft model; female NOD/SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallography assay
• Experiment for Drug Resistance: CellTiter-96 AQueous One assay

Ripretinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [29]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Drug: Ripretinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [29]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Drug: Ripretinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

Rucaparib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [36]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Sensitive Drug: Rucaparib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

Ruxolitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [37]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L857P (c.2570T>C)
• Resistant Drug: Ruxolitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [37]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V674A (c.2021T>C)
• Sensitive Drug: Ruxolitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [38]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N610H (c.1828A>C)
• Sensitive Drug: Ruxolitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: C57/BL6 mouse model; Mus musculus
• Experiment for Molecule Alteration: Sanger genomic DNA sequencing assay
• Experiment for Drug Resistance: MTS assay

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [39]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T640N (c.1919C>A)
• Sensitive Drug: Ruxolitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T17 cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Sanger sequencing assay; Western blotting analysis
• Experiment for Drug Resistance: Cytokine-independent growth assay

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [38]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N610S (c.1829A>G)
• Sensitive Drug: Ruxolitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: C57/BL6 mouse model; Mus musculus
• Experiment for Molecule Alteration: Sanger genomic DNA sequencing assay
• Experiment for Drug Resistance: MTS assay

Selpercatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [40]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M918T (c.2753T>C)
• Sensitive Drug: Selpercatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vivo Model: mouse PDX model; Mus musculus
• Mechanism Description: LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations.

Sonidegib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I408V (c.1222A>G)
• Resistant Drug: Sonidegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.I408V (c.1222A>G) in gene SMO cause the resistance of Sonidegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.A459V (c.1376C>T)
• Resistant Drug: Sonidegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.A459V (c.1376C>T) in gene SMO cause the resistance of Sonidegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C469Y (c.1406G>A)
• Resistant Drug: Sonidegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.C469Y (c.1406G>A) in gene SMO cause the resistance of Sonidegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T241M (c.722C>T)
• Resistant Drug: Sonidegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.T241M (c.722C>T) in gene SMO cause the resistance of Sonidegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W281C (c.843G>T)
• Resistant Drug: Sonidegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.W281C (c.843G>T) in gene SMO cause the resistance of Sonidegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V321M (c.961G>A)
• Resistant Drug: Sonidegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.V321M (c.961G>A) in gene SMO cause the resistance of Sonidegib by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [42]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D384N (c.1150G>A)
• Resistant Drug: Sonidegib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Hippo signaling pathway; Inhibition; hsa04390
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: HEK293S cells; Fetal kidney; Homo sapiens (Human); CVCL_A784
• In Vivo Model: NOD/SCID mouse; Mus musculus
• Experiment for Molecule Alteration: Immunofluorescence imaging assay
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: Posaconazole inhibits the Hh pathway by a mechanism distinct from that of cyclopamine and other cyclopamine-competitive SMO antagonists but similar to itraconazole, has robust activity against drug-resistant SMO mutants and inhibits the growth of Hh-dependent basal cell carcinoma in vivo.

Key Molecule: Smoothened homolog (SMO) [42]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.S387N (c.1160G>A)
• Resistant Drug: Sonidegib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Hippo signaling pathway; Inhibition; hsa04390
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: HEK293S cells; Fetal kidney; Homo sapiens (Human); CVCL_A784
• In Vivo Model: NOD/SCID mouse; Mus musculus
• Experiment for Molecule Alteration: Immunofluorescence imaging assay
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: Posaconazole inhibits the Hh pathway by a mechanism distinct from that of cyclopamine and other cyclopamine-competitive SMO antagonists but similar to itraconazole, has robust activity against drug-resistant SMO mutants and inhibits the growth of Hh-dependent basal cell carcinoma in vivo.

Key Molecule: Smoothened homolog (SMO) [42]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E518K (c.1552G>A)
• Resistant Drug: Sonidegib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Hippo signaling pathway; Inhibition; hsa04390
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: HEK293S cells; Fetal kidney; Homo sapiens (Human); CVCL_A784
• In Vivo Model: NOD/SCID mouse; Mus musculus
• Experiment for Molecule Alteration: Immunofluorescence imaging assay
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: Posaconazole inhibits the Hh pathway by a mechanism distinct from that of cyclopamine and other cyclopamine-competitive SMO antagonists but similar to itraconazole, has robust activity against drug-resistant SMO mutants and inhibits the growth of Hh-dependent basal cell carcinoma in vivo.

Key Molecule: Smoothened homolog (SMO) [42]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N219D (c.655A>G)
• Resistant Drug: Sonidegib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Hippo signaling pathway; Inhibition; hsa04390
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: HEK293S cells; Fetal kidney; Homo sapiens (Human); CVCL_A784
• In Vivo Model: NOD/SCID mouse; Mus musculus
• Experiment for Molecule Alteration: Immunofluorescence imaging assay
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: Posaconazole inhibits the Hh pathway by a mechanism distinct from that of cyclopamine and other cyclopamine-competitive SMO antagonists but similar to itraconazole, has robust activity against drug-resistant SMO mutants and inhibits the growth of Hh-dependent basal cell carcinoma in vivo.

Tazemetostat

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [43]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y111D (c.331T>G)
• Resistant Drug: Tazemetostat
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Pfeiffer cells; Pleural effusion; Homo sapiens (Human); CVCL_3326
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Tegafur

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Dihydropyrimidine dehydrogenase [NADP(+)] [44]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I560S (c.1679T>G)
• Sensitive Drug: Tegafur
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Dihydropyrimidine dehydrogenase [NADP(+)] [44]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D949V (c.2846A>T)
• Sensitive Drug: Tegafur
• Experimental Note: Identified from the Human Clinical Data

Tepotinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1003F (c.3008A>T)
• Sensitive Drug: Tepotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1010Y (c.3028G>T)
• Sensitive Drug: Tepotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Tofacitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [37]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L857P (c.2570T>C)
• Sensitive Drug: Tofacitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [45]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E183G (c.548A>G)
• Sensitive Drug: Tofacitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.E183G (c.548A>G) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [37]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V674A (c.2021T>C)
• Sensitive Drug: Tofacitinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [45]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.A572V (c.1715C>T)
• Sensitive Drug: Tofacitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.A572V (c.1715C>T) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [45]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L156P (c.467T>C)
• Sensitive Drug: Tofacitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.L156P (c.467T>C) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [45]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R172Q (c.515G>A)
• Sensitive Drug: Tofacitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.R172Q (c.515G>A) in gene JAK3 cause the sensitivity of Tofacitinib by aberration of the drug's therapeutic target

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [46]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V722I (c.2164G>A)
• Sensitive Drug: Tofacitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue exclusion assay

Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [47]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [48]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F247L (c.739T>C)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Activation; hsa04010
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMLER cells; Breast; Homo sapiens (Human); CVCL_DG85
• In Vivo Model: Athymic mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay; Immunofluorescence assay; qPCR
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Reseachers identified an oncogenic mutation, F247L, whose expression robustly activated the MAPK pathway and sensitized cells to BRAF and MEK inhibitors.

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [49]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y288C (c.863A>G)
• Sensitive Drug: Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Presto blue assay
• Mechanism Description: PDGFRA Y288C induces constitutive phosphorylation of Akt, ERK1/2, and STAT3. PDGFRA Y288C is resistant to PDGFR inhibitors, such as crenolanib, but sensitive to PI3K/mTOR and MEK inhibitors, such as omipalisib, consistent with pathway activation results.

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [50]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L597S (c.1789_1790delCTinsTC)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Melanoma thyroid metastasis; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.L597S (c.1789_1790delCTinsTC) in gene BRAF cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [50]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L597R (c.1790T>G)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Melanoma thyroid metastasis; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.L597R (c.1790T>G) in gene BRAF cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [50]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K601E (c.1801A>G)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Melanoma thyroid metastasis; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.K601E (c.1801A>G) in gene BRAF cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [38]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N610S (c.1829A>G)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: C57/BL6 mouse model; Mus musculus
• Experiment for Molecule Alteration: Sanger genomic DNA sequencing assay
• Experiment for Drug Resistance: MTS assay

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [38]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N610H (c.1828A>C)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: C57/BL6 mouse model; Mus musculus
• Experiment for Molecule Alteration: Sanger genomic DNA sequencing assay
• Experiment for Drug Resistance: MTS assay

Key Molecule: PI3-kinase alpha (PIK3CA) [51]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N345K (c.1035T>G)
• Sensitive Drug: Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.N345K (c.1035T>G) in gene PIK3CA cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [51]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Drug: Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [51]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q546K (c.1636C>A)
• Sensitive Drug: Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.Q546K (c.1636C>A) in gene PIK3CA cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [51]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Drug: Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [51]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G1049R (c.3145G>C)
• Sensitive Drug: Trametinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.G1049R (c.3145G>C) in gene PIK3CA cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Tucatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• Resistant Drug: Tucatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Resistant Drug: Tucatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)
• Resistant Drug: Tucatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Vandetanib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V804M (c.2410G>A)
• Resistant Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.V804M (c.2410G>A) in gene RET cause the resistance of Vandetanib by aberration of the drug's therapeutic target

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V804L (c.2410G>C)
• Resistant Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.V804L (c.2410G>C) in gene RET cause the resistance of Vandetanib by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C634R (c.1900T>C)
• Sensitive Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.C634R (c.1900T>C) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E768D (c.2304G>C)
• Sensitive Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.E768D (c.2304G>C) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L790F (c.2370G>T)
• Sensitive Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.L790F (c.2370G>T) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y791F (c.2372A>T)
• Sensitive Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.Y791F (c.2372A>T) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.A883F (c.2647_2648delGCinsTT)
• Sensitive Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.A883F (c.2647_2648delGCinsTT) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.S891A (c.2671T>G)
• Sensitive Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.S891A (c.2671T>G) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [52]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M918T (c.2753T>C)
• Sensitive Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Growth curves and transformation assay
• Mechanism Description: The missense mutation p.M918T (c.2753T>C) in gene RET cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase ABL1 (ABL1) [14]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V299L (c.895G>C)
• Sensitive Drug: Vandetanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ph+ALL cells; N.A.; .; N.A.
• Mechanism Description: The missense mutation p.V299L (c.895G>C) in gene ABL1 cause the sensitivity of Vandetanib by aberration of the drug's therapeutic target

Vardenafil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [53]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Vardenafil
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SJG 2 cells; Ora cavity; Homo sapiens (Human); CVCL_WV26
• In Vitro Model: ATCC 293T cells; Fetal kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis; Immunofluorescence analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Vardenafil reverses ABCB1-mediated MDR by directly blocking the drug efflux function of ABCB1.

Clinical Trial Drug(s) 41 drug(s) in total

Capivasertib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [54]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Drug: Capivasertib
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Capivasertib by aberration of the drug's therapeutic target

Cediranib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Sensitive Drug: Cediranib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Sensitive Drug: Cediranib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Sensitive Drug: Cediranib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of Cediranib by aberration of the drug's therapeutic target

Cobimetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [5]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Drug: Cobimetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: Phoenix AMPHO cells; Fetal kidney; Homo sapiens (Human); CVCL_H716
• In Vivo Model: NOD scid gamma xenograft model; Mus musculus
• Experiment for Molecule Alteration: Single cell sequencing assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [55]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.N486_T491delinsK (c.1458_1472del15)
• Sensitive Drug: Cobimetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [56]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: Cobimetinib
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of Cobimetinib by unusual activation of pro-survival pathway

Crenolanib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [49]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y288C (c.863A>G)
• Resistant Drug: Crenolanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Presto blue assay
• Mechanism Description: PDGFRA Y288C induces constitutive phosphorylation of Akt, ERK1/2, and STAT3. PDGFRA Y288C is resistant to PDGFR inhibitors, such as crenolanib, but sensitive to PI3K/mTOR and MEK inhibitors, such as omipalisib, consistent with pathway activation results.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [49]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Drug: Crenolanib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BaF3 cells; Bone; Mus musculus (Mouse); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: XTT assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [49]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V561D (c.1682T>A)
• Sensitive Drug: Crenolanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Presto blue assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [57]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.P577S (c.1729C>T)
• Sensitive Drug: Crenolanib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.P577S (c.1729C>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [57]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V658A (c.1973T>C)
• Sensitive Drug: Crenolanib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.V658A (c.1973T>C) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [57]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R841K (c.2522G>A)
• Sensitive Drug: Crenolanib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.R841K (c.2522G>A) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [57]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D842Y (c.2524G>T)
• Sensitive Drug: Crenolanib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.D842Y (c.2524G>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [57]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H845Y (c.2533C>T)
• Sensitive Drug: Crenolanib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.H845Y (c.2533C>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [57]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G853D (c.2558G>A)
• Sensitive Drug: Crenolanib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.G853D (c.2558G>A) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [58]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N659K (c.1977C>G)
• Sensitive Drug: Crenolanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Biochemical assessment of PDGFRA/KIT kinase activity assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: The missense mutation p.N659K (c.1977C>G) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Ganetespib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: Ganetespib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Cellular tumor antigen p53 (TP53) [59]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R248Q (c.743G>A)
• Sensitive Drug: Ganetespib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-46 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vitro Model: EFO21 cells; Ascites; Homo sapiens (Human); CVCL_0029
• In Vitro Model: COV434 cells; N.A.; Homo sapiens (Human); CVCL_2010
• In Vitro Model: COLO704 cells; Ascites; Homo sapiens (Human); CVCL_1994
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vivo Model: Athymic (nu/nu) male xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Quantitative PCR analysis
• Experiment for Drug Resistance: CellTiter-blue cell viability assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
• Sensitive Drug: Ganetespib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
• Sensitive Drug: Ganetespib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Nazartinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [60]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Sensitive Drug: Nazartinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor

Key Molecule: Epidermal growth factor receptor (EGFR) [60]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.N771_H773 (c.2311_2319)
• Sensitive Drug: Nazartinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor

Niraparib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [36]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Sensitive Drug: Niraparib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

Rigosertib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [61]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G12V (c.35G>T)
• Sensitive Drug: Rigosertib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: RAS/RAF/MEK/ERK signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: WM1617 cells; Lymph node; Homo sapiens (Human); CVCL_6791
• In Vivo Model: Female nu/nu mouse PDX model; Mus musculus
• Mechanism Description: Rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that rigosertib binds to the RBDs of Ral-GDS and PI3Ks.

Key Molecule: PI3-kinase alpha (PIK3CA) [61]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Drug: Rigosertib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: RAS/RAF/MEK/ERK signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: WM1617 cells; Lymph node; Homo sapiens (Human); CVCL_6791
• In Vivo Model: Female nu/nu mouse PDX model; Mus musculus
• Mechanism Description: Rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that rigosertib binds to the RBDs of Ral-GDS and PI3Ks.

Key Molecule: PI3-kinase alpha (PIK3CA) [61]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Drug: Rigosertib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: RAS/RAF/MEK/ERK signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: WM1617 cells; Lymph node; Homo sapiens (Human); CVCL_6791
• In Vivo Model: Female nu/nu mouse PDX model; Mus musculus
• Mechanism Description: Rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that rigosertib binds to the RBDs of Ral-GDS and PI3Ks.

Selumetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Drug: Selumetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of Selumetinib by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Sensitive Drug: Selumetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Drug: Selumetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Sensitive Drug: Selumetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Sensitive Drug: Selumetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Sensitive Drug: Selumetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Sensitive Drug: Selumetinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Tivantinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1010Y (c.3028G>T)
• Resistant Drug: Tivantinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1003F (c.3008A>T)
• Resistant Drug: Tivantinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

AZD-4547

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [62]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V564F (c.1690G>T)
• Resistant Drug: AZD-4547
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Resistant Drug: AZD-4547
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the resistance of AZD-4547 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [22]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Resistant Drug: AZD-4547
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Resistant Drug: AZD-4547
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of AZD-4547 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [22]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Resistant Drug: AZD-4547
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Promega assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W290C (c.870G>T)
• Sensitive Drug: AZD-4547
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.W290C (c.870G>T) in gene FGFR2 cause the sensitivity of AZD-4547 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Sensitive Drug: AZD-4547
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the sensitivity of AZD-4547 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [24]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Sensitive Drug: AZD-4547
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay
• Mechanism Description: The missense mutation p.K660N (c.1980G>C) in gene FGFR2 cause the sensitivity of AZD-4547 by aberration of the drug's therapeutic target

Afabicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
• Resistant Drug: Afabicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: Afabicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• Sensitive Drug: Afabicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Apitolisib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [63]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Drug: Apitolisib
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DxS allele-specific PCR; qRT-PCR assays; Sanger sequencing assay
• Experiment for Drug Resistance: CTCAE assay

AUY922

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [64]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Sensitive Drug: AUY922
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Key Molecule: Epidermal growth factor receptor (EGFR) [64]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.Y764_V765insHH (c.2292_2293insCATCAT)
• Sensitive Drug: AUY922
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Key Molecule: Epidermal growth factor receptor (EGFR) [64]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Sensitive Drug: AUY922
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Key Molecule: Epidermal growth factor receptor (EGFR) [64]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.P772_H773insGNP (c.2316_2317insGGTAACCCT)
• Sensitive Drug: AUY922
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Key Molecule: Epidermal growth factor receptor (EGFR) [64]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.H773 (c.2317_2319)
• Sensitive Drug: AUY922
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: EGFR exon 20 insertion mutants associate with the heat shock protein 90 (Hsp90) chaperone system. The non-geldanamycin Hsp90 inhibitor luminespib (formerly AUY922) degrades EGFR exon 20 mutations, downstream targets and induces apoptosis.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• Sensitive Drug: AUY922
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: AUY922
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
• Sensitive Drug: AUY922
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

DEBIO-1347

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [62]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V564I (c.1690G>A)
• Resistant Drug: DEBIO-1347
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [62]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V564L (c.1690G>C)
• Resistant Drug: DEBIO-1347
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Resistant Drug: DEBIO-1347
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of DEBIO-1347 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Resistant Drug: DEBIO-1347
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of DEBIO-1347 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Resistant Drug: DEBIO-1347
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the resistance of DEBIO-1347 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [62]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V564F (c.1690G>T)
• Sensitive Drug: DEBIO-1347
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 327 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Sensitive Drug: DEBIO-1347
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of DEBIO-1347 by aberration of the drug's therapeutic target

Flumatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.I571_D579 (c.1711_1737)
• Resistant Drug: Flumatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 32D cells; Bone marrow; Homo sapiens (Human); CVCL_0118
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The duplication p.I571_D579 (c.1711_1737) in gene KIT cause the resistance of Flumatinib by aberration of the drug's therapeutic target.

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816Y (c.2446G>T)
• Resistant Drug: Flumatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IL-3-dependent murine hematopoietic cells; Blood; Mus musculus (Mouse); CVCL_2015
• In Vitro Model: IL-3-dependent murine hematopoietic cells; Blood; Mus musculus (Mouse); CVCL_2015
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Resistant Drug: Flumatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IL-3-dependent murine hematopoietic cells; Blood; Mus musculus (Mouse); CVCL_2015
• In Vitro Model: IL-3-dependent murine hematopoietic cells; Blood; Mus musculus (Mouse); CVCL_2015
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.T417_D419delinsI (c.1249_1257delinsATC)
• Sensitive Drug: Flumatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 32D cells; Bone marrow; Homo sapiens (Human); CVCL_0118
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The complex-indel p.T417_D419delinsI (c.1249_1257delinsATC) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target.

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.A502_Y503 (c.1504_1509)
• Sensitive Drug: Flumatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 32D cells; Bone marrow; Homo sapiens (Human); CVCL_0118
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The duplication p.A502_Y503 (c.1504_1509) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target.

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.V559_V560delVV (c.1676_1681delTTGTTG)
• Sensitive Drug: Flumatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 32D cells; Bone marrow; Homo sapiens (Human); CVCL_0118
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The if-deletion p.V559_V560delVV (c.1676_1681delTTGTTG) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target.

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N822K (c.2466T>G)
• Sensitive Drug: Flumatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 32D cells; Bone marrow; Homo sapiens (Human); CVCL_0118
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.N822K (c.2466T>G) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V559D (c.1676T>A)
• Sensitive Drug: Flumatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 32D cells; Bone marrow; Homo sapiens (Human); CVCL_0118
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.V559D (c.1676T>A) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [10]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816H (c.2446G>C)
• Sensitive Drug: Flumatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 32D cells; Bone marrow; Homo sapiens (Human); CVCL_0118
• In Vivo Model: Female Balb/cA-nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.D816H (c.2446G>C) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target

Foretinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase ABL1 (ABL1) [14]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V299L (c.895G>C)
• Sensitive Drug: Foretinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ph+ALL cells; N.A.; .; N.A.
• Mechanism Description: The missense mutation p.V299L (c.895G>C) in gene ABL1 cause the sensitivity of Foretinib by aberration of the drug's therapeutic target

LY-2874455

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Resistant Drug: LY-2874455
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of LY-2874455 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Sensitive Drug: LY-2874455
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Sensitive Drug: LY-2874455
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Sensitive Drug: LY-2874455
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target

Merestinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1010Y (c.3028G>T)
• Sensitive Drug: Merestinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1003F (c.3008A>T)
• Sensitive Drug: Merestinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Hepatocyte growth factor receptor (MET) [65]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228N (c.3682G>A)
• Sensitive Drug: Merestinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Calu1 cells; Lung; Homo sapiens (Human); CVCL_0608
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: U118 MG cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: H441 cells; Pericardial effusion; Homo sapiens (Human); CVCL_1561
• In Vitro Model: H1993 cells; Lymph node; Homo sapiens (Human); CVCL_1512
• In Vivo Model: Athymic nude mouse and CD-1 nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.D1228N (c.3682G>A) in gene MET cause the sensitivity of Merestinib by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [65]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230C (c.3689A>G)
• Sensitive Drug: Merestinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Calu1 cells; Lung; Homo sapiens (Human); CVCL_0608
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: U118 MG cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: H441 cells; Pericardial effusion; Homo sapiens (Human); CVCL_1561
• In Vitro Model: H1993 cells; Lymph node; Homo sapiens (Human); CVCL_1512
• In Vivo Model: Athymic nude mouse and CD-1 nude mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.Y1230C (c.3689A>G) in gene MET cause the sensitivity of Merestinib by aberration of the drug's therapeutic target

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Hepatocyte growth factor receptor (MET) [13]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228V (c.3683A>T)
• Sensitive Drug: Merestinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: There is a patient with metastatic NSCLC with MET-mediated resistance to EGFR TKI who responded to treatment with a type I MET inhibitor, savolitinib, given in combination with a third-generation EGFR inhibitor, osimertinib. The patient then developed acquired resistance mediated by a novel MET kinase domain mutation.

Naquotinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [66]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.Y764_V765insHH (c.2292_2293insCATCAT)
• Resistant Drug: Naquotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [66]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.L747_P753delinsS (c.2240_2257del18)
• Sensitive Drug: Naquotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [66]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Sensitive Drug: Naquotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [66]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.A767_V769 (c.2299_2307)
• Sensitive Drug: Naquotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [66]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.P772_H773insGNP (c.2316_2317insGGTAACCCT)
• Sensitive Drug: Naquotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

Key Molecule: Epidermal growth factor receptor (EGFR) [66]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: Naquotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9ER cells; N.A.; .; N.A.
• In Vitro Model: BID007 cells; Pleural effusion; Homo sapiens (Human); CVCL_W890
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: MTS assay; FACS assay
• Mechanism Description: There is a mechanism for resistance associated with EGFR Y764_V765insHH mutation, one of the most resistant mutations. We demonstrated that in Y764_V765insHH, histidine residues inserted in the Val765 and Met766 positions upregulated the EGFR kinase activity and caused steric insensitivity to the particular EGFR-TKIs.

PLX8394

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [67]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Synonymous; p.K601K (c.1803A>G)
• Sensitive Drug: PLX8394
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [67]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Synonymous; p.G464G (c.1392A>T)
• Sensitive Drug: PLX8394
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [67]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G469R (c.1405G>A)
• Sensitive Drug: PLX8394
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [67]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G469A (c.1406G>C)
• Sensitive Drug: PLX8394
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [67]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G469V (c.1406G>T)
• Sensitive Drug: PLX8394
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [67]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Synonymous; p.L597L (c.1791A>T)
• Sensitive Drug: PLX8394
• Experimental Note: Identified from the Human Clinical Data

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [68]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: PLX8394
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PRT cells; Brain; Homo sapiens (Human); CVCL_7207
• In Vitro Model: 1205Lu cells; Skin; Homo sapiens (Human); CVCL_5239
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay; AlamarBlue assay; Colony growth assay

Poziotinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The if-insertion p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT) in gene EGFR cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Epidermal growth factor receptor (EGFR) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.A767_V769 (c.2299_2307)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The duplication p.A767_V769 (c.2299_2307) in gene EGFR cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Epidermal growth factor receptor (EGFR) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The duplication p.S768_D770 (c.2302_2310) in gene EGFR cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Epidermal growth factor receptor (EGFR) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.N771_H773 (c.2311_2319)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The duplication p.N771_H773 (c.2311_2319) in gene EGFR cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Epidermal growth factor receptor (EGFR) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.P772_H773insGNP (c.2316_2317insGGTAACCCT)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The if-insertion p.P772_H773insGNP (c.2316_2317insGGTAACCCT) in gene EGFR cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The duplication p.Y772_A775 (c.2314_2325) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVV (c.2326_2328delinsGTAGTA)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The complex-indel p.G776_776delinsVV (c.2326_2328delinsGTAGTA) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The complex-indel p.G776_776delinsVC (c.2326_2328delinsGTATGT) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [69]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)
• Sensitive Drug: Poziotinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: CUTO14 cells; N.A.; .; N.A.
• In Vivo Model: Female nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer Glo assay
• Mechanism Description: The duplication p.G778_P780 (c.2332_2340) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• Sensitive Drug: Poziotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

RAF-265

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [70]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: RAF-265
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: BRAF kinase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of RAF-265 by aberration of the drug's therapeutic target

Sapitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L869R (c.2606T>G)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L755S (c.2263_2264delCTinsAG)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L755P (c.2264T>C)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D769N (c.2305G>A)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D769H (c.2305G>C)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D769Y (c.2305G>T)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V773M (c.2317G>A)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsLC (c.2326_2328delinsCTTTGT)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVV (c.2326_2328delinsGTAGTA)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V777L (c.2329G>C)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.G778_S779insLPS (c.2334_2335insCTTCCTAGC)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L786V (c.2356C>G)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [71]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V842I (c.2524G>A)
• Resistant Drug: Sapitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: CW-2 cells; Colon; Homo sapiens (Human); CVCL_1151
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model; Mus musculus
• Experiment for Drug Resistance: Cell Titer Glo assay

Uprosertib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [72]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Drug: Uprosertib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vivo Model: Female nu/nu CD-1 mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Uprosertib by aberration of the drug's therapeutic target

AEE-788

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [73]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N826S (c.2477A>G)
• Resistant Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter96 Proliferation assay
• Mechanism Description: The missense mutation p.N826S (c.2477A>G) in gene EGFR cause the resistance of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L755S (c.2263_2264delCTinsAG)
• Resistant Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the resistance of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L755P (c.2264T>C)
• Resistant Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the resistance of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T798M (c.2393_2394delCAinsTG)
• Resistant Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the resistance of AEE-788 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [73]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.L747_P753delinsS (c.2240_2257del18)
• Sensitive Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter96 Proliferation assay
• Mechanism Description: The complex-indel p.L747_P753delinsS (c.2240_2257del18) in gene EGFR cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target.

Key Molecule: Epidermal growth factor receptor (EGFR) [73]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter96 Proliferation assay
• Mechanism Description: The missense mutation p.L858R (c.2573T>G) in gene EGFR cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V773A (c.2318T>C)
• Sensitive Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.V773A (c.2318T>C) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V777L (c.2329G>C)
• Sensitive Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.V777L (c.2329G>C) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N857S (c.2570A>G)
• Sensitive Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.N857S (c.2570A>G) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T862A (c.2584A>G)
• Sensitive Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.T862A (c.2584A>G) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H878Y (c.2632C>T)
• Sensitive Drug: AEE-788
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.H878Y (c.2632C>T) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

BMS-777607

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Hepatocyte growth factor receptor (MET) [12]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230H (c.3688T>C)
• Sensitive Drug: BMS-777607
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Athymic female mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MET mutations Y1248H and D1246N are resistance mechanisms for type I MET-TKIs. NIH3T3 cells expressing either mutation showed resistance to both INC280 and crizotinib but not cabozantinib, indicating the potential of sequential use of MET inhibitors may lead to a more durable response.

Key Molecule: Hepatocyte growth factor receptor (MET) [12]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228N (c.3682G>A)
• Sensitive Drug: BMS-777607
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Athymic female mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MET mutations Y1248H and D1246N are resistance mechanisms for type I MET-TKIs. NIH3T3 cells expressing either mutation showed resistance to both INC280 and crizotinib but not cabozantinib, indicating the potential of sequential use of MET inhibitors may lead to a more durable response.

Lifirafenib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [75]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: Lifirafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• In Vitro Model: WiDR cells; Colon; Homo sapiens (Human); CVCL_2760
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vivo Model: Female NOD/SCID and BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Tumor volume measurement assay

Key Molecule: Epidermal growth factor receptor (EGFR) [75]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: Lifirafenib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• In Vitro Model: WiDR cells; Colon; Homo sapiens (Human); CVCL_2760
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vivo Model: Female NOD/SCID and BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Tumor volume measurement assay

Taladegib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I408V (c.1222A>G)
• Resistant Drug: Taladegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.I408V (c.1222A>G) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.A459V (c.1376C>T)
• Resistant Drug: Taladegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.A459V (c.1376C>T) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C469Y (c.1406G>A)
• Resistant Drug: Taladegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.C469Y (c.1406G>A) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T241M (c.722C>T)
• Resistant Drug: Taladegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.T241M (c.722C>T) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W281C (c.843G>T)
• Resistant Drug: Taladegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.W281C (c.843G>T) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V321M (c.961G>A)
• Resistant Drug: Taladegib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.V321M (c.961G>A) in gene SMO cause the resistance of Taladegib by aberration of the drug's therapeutic target

Altiratinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Hepatocyte growth factor receptor (MET) [76]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228N (c.3682G>A)
• Sensitive Drug: Altiratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: Sk-N-SH cells; Adrenal; Homo sapiens (Human); CVCL_0531
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: EBC-1 cells; Lung; Homo sapiens (Human); CVCL_2891
• In Vitro Model: MRC-5 cells; Lung; Homo sapiens (Human); CVCL_0440
• In Vitro Model: PC-3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: SkMEL5 cells; Skin; Homo sapiens (Human); CVCL_0527
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: M-NFS-60 cells; Blood; Mus musculus (Mouse); CVCL_3543
• In Vitro Model: KM-12 cells; Colon; Homo sapiens (Human); CVCL_1331
• In Vitro Model: HMVEC cells; Blood vessel; Homo sapiens (Human); N.A.
• In Vitro Model: EAhy926 cells; N.A.; Homo sapiens (Human); CVCL_3901
• In Vitro Model: CHO-K cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0213
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: B16/F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Mouse xenograft efficacy model; MKN-45 xenograft mouse pharmacokinetic/pharmacodynamic model; Orthotopic U87-MG xenograft efficacy model; Orthotopic U87-MG xenograft survival model; PyMT syngeneic breast cancer model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay; Western blotting analysis
• Experiment for Drug Resistance: Resazurin cell viability assay

Key Molecule: Hepatocyte growth factor receptor (MET) [76]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230H (c.3688T>C)
• Sensitive Drug: Altiratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: Sk-N-SH cells; Adrenal; Homo sapiens (Human); CVCL_0531
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: EBC-1 cells; Lung; Homo sapiens (Human); CVCL_2891
• In Vitro Model: MRC-5 cells; Lung; Homo sapiens (Human); CVCL_0440
• In Vitro Model: PC-3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: SkMEL5 cells; Skin; Homo sapiens (Human); CVCL_0527
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: M-NFS-60 cells; Blood; Mus musculus (Mouse); CVCL_3543
• In Vitro Model: KM-12 cells; Colon; Homo sapiens (Human); CVCL_1331
• In Vitro Model: HMVEC cells; Blood vessel; Homo sapiens (Human); N.A.
• In Vitro Model: EAhy926 cells; N.A.; Homo sapiens (Human); CVCL_3901
• In Vitro Model: CHO-K cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0213
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: B16/F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Mouse xenograft efficacy model; MKN-45 xenograft mouse pharmacokinetic/pharmacodynamic model; Orthotopic U87-MG xenograft efficacy model; Orthotopic U87-MG xenograft survival model; PyMT syngeneic breast cancer model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay; Western blotting analysis
• Experiment for Drug Resistance: Resazurin cell viability assay

Key Molecule: Hepatocyte growth factor receptor (MET) [76]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230D (c.3688T>G)
• Sensitive Drug: Altiratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: Sk-N-SH cells; Adrenal; Homo sapiens (Human); CVCL_0531
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: EBC-1 cells; Lung; Homo sapiens (Human); CVCL_2891
• In Vitro Model: MRC-5 cells; Lung; Homo sapiens (Human); CVCL_0440
• In Vitro Model: PC-3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: SkMEL5 cells; Skin; Homo sapiens (Human); CVCL_0527
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: M-NFS-60 cells; Blood; Mus musculus (Mouse); CVCL_3543
• In Vitro Model: KM-12 cells; Colon; Homo sapiens (Human); CVCL_1331
• In Vitro Model: HMVEC cells; Blood vessel; Homo sapiens (Human); N.A.
• In Vitro Model: EAhy926 cells; N.A.; Homo sapiens (Human); CVCL_3901
• In Vitro Model: CHO-K cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0213
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: B16/F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Mouse xenograft efficacy model; MKN-45 xenograft mouse pharmacokinetic/pharmacodynamic model; Orthotopic U87-MG xenograft efficacy model; Orthotopic U87-MG xenograft survival model; PyMT syngeneic breast cancer model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay; Western blotting analysis
• Experiment for Drug Resistance: Resazurin cell viability assay

Key Molecule: Hepatocyte growth factor receptor (MET) [76]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230C (c.3689A>G)
• Sensitive Drug: Altiratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: Sk-N-SH cells; Adrenal; Homo sapiens (Human); CVCL_0531
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: EBC-1 cells; Lung; Homo sapiens (Human); CVCL_2891
• In Vitro Model: MRC-5 cells; Lung; Homo sapiens (Human); CVCL_0440
• In Vitro Model: PC-3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: SkMEL5 cells; Skin; Homo sapiens (Human); CVCL_0527
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: M-NFS-60 cells; Blood; Mus musculus (Mouse); CVCL_3543
• In Vitro Model: KM-12 cells; Colon; Homo sapiens (Human); CVCL_1331
• In Vitro Model: HMVEC cells; Blood vessel; Homo sapiens (Human); N.A.
• In Vitro Model: EAhy926 cells; N.A.; Homo sapiens (Human); CVCL_3901
• In Vitro Model: CHO-K cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0213
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: B16/F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Mouse xenograft efficacy model; MKN-45 xenograft mouse pharmacokinetic/pharmacodynamic model; Orthotopic U87-MG xenograft efficacy model; Orthotopic U87-MG xenograft survival model; PyMT syngeneic breast cancer model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay; Western blotting analysis
• Experiment for Drug Resistance: Resazurin cell viability assay

Key Molecule: Hepatocyte growth factor receptor (MET) [76]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M1250T (c.3749T>C)
• Sensitive Drug: Altiratinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: Sk-N-SH cells; Adrenal; Homo sapiens (Human); CVCL_0531
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: EBC-1 cells; Lung; Homo sapiens (Human); CVCL_2891
• In Vitro Model: MRC-5 cells; Lung; Homo sapiens (Human); CVCL_0440
• In Vitro Model: PC-3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: HUVEC cells; Endothelium; Homo sapiens (Human); N.A.
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: SkMEL5 cells; Skin; Homo sapiens (Human); CVCL_0527
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: M-NFS-60 cells; Blood; Mus musculus (Mouse); CVCL_3543
• In Vitro Model: KM-12 cells; Colon; Homo sapiens (Human); CVCL_1331
• In Vitro Model: HMVEC cells; Blood vessel; Homo sapiens (Human); N.A.
• In Vitro Model: EAhy926 cells; N.A.; Homo sapiens (Human); CVCL_3901
• In Vitro Model: CHO-K cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0213
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: B16/F10 cells; Skin; Mus musculus (Mouse); CVCL_0159
• In Vivo Model: Mouse xenograft efficacy model; MKN-45 xenograft mouse pharmacokinetic/pharmacodynamic model; Orthotopic U87-MG xenograft efficacy model; Orthotopic U87-MG xenograft survival model; PyMT syngeneic breast cancer model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay; Western blotting analysis
• Experiment for Drug Resistance: Resazurin cell viability assay

Berzosertib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [36]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Sensitive Drug: Berzosertib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

GSK126

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [43]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y111D (c.331T>G)
• Resistant Drug: GSK126
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Pfeiffer cells; Pleural effusion; Homo sapiens (Human); CVCL_3326
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

JQ1

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [41]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.A459V (c.1376C>T)
• Sensitive Drug: JQ1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.A459V (c.1376C>T) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C469Y (c.1406G>A)
• Sensitive Drug: JQ1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.C469Y (c.1406G>A) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T241M (c.722C>T)
• Sensitive Drug: JQ1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.T241M (c.722C>T) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W281C (c.843G>T)
• Sensitive Drug: JQ1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.W281C (c.843G>T) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Key Molecule: Smoothened homolog (SMO) [41]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V321M (c.961G>A)
• Sensitive Drug: JQ1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Basal cell carcinoma tissue; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: SNP and CGH array assay
• Mechanism Description: The missense mutation p.V321M (c.961G>A) in gene SMO cause the sensitivity of JQ1 by aberration of the drug's therapeutic target

Lazertinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [77]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: Lazertinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: PC9GR cells; Lung; Homo sapiens (Human); CVCL_V337
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: H2291 cells; Lung; Homo sapiens (Human); CVCL_1546
• In Vivo Model: Female BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Sanger sequencing assay
• Experiment for Drug Resistance: Cell-free kinase assay; IC50 assay

LY3009120

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [78]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.L485_P490delLNVTAP (c.1453_1470del18)
• Sensitive Drug: LY3009120
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: OV-90 cells; Ascites; Homo sapiens (Human); CVCL_3768
• In Vitro Model: H2405 cells; Lung; Homo sapiens (Human); CVCL_1551
• In Vivo Model: NIH nude rat xenograft model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay

MRX-2843

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [79]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D835V (c.2504A>T)
• Sensitive Drug: MRX-2843
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: MOLM-14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: NOMO-1 cells; Bone marrow; Homo sapiens (Human); CVCL_1609
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: MRX-2843, a type 1 small-molecule tyrosine kinase inhibitor that abrogates activation of both MERTK and FLT3 and their downstream effectors. MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD, with a wide therapeutic window compared with that of normal human cord blood cells.

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [79]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D835Y (c.2503G>T)
• Sensitive Drug: MRX-2843
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: MOLM-14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: NOMO-1 cells; Bone marrow; Homo sapiens (Human); CVCL_1609
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: MRX-2843, a type 1 small-molecule tyrosine kinase inhibitor that abrogates activation of both MERTK and FLT3 and their downstream effectors. MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD, with a wide therapeutic window compared with that of normal human cord blood cells.

Omipalisib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [49]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Drug: Omipalisib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Presto blue assay
• Mechanism Description: PDGFRA Y288C induces constitutive phosphorylation of Akt, ERK1/2, and STAT3. PDGFRA Y288C is resistant to PDGFR inhibitors, such as crenolanib, but sensitive to PI3K/mTOR and MEK inhibitors, such as omipalisib, consistent with pathway activation results.

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [49]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y288C (c.863A>G)
• Sensitive Drug: Omipalisib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Presto blue assay
• Mechanism Description: PDGFRA Y288C induces constitutive phosphorylation of Akt, ERK1/2, and STAT3. PDGFRA Y288C is resistant to PDGFR inhibitors, such as crenolanib, but sensitive to PI3K/mTOR and MEK inhibitors, such as omipalisib and trametinib, consistent with pathway activation results.

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [49]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V561D (c.1682T>A)
• Sensitive Drug: Omipalisib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Presto blue assay

PLX4720

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [70]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: PLX4720
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: BRAF kinase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of PLX4720 by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Sensitive Drug: PLX4720
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Drug: PLX4720
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Sensitive Drug: PLX4720
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Sensitive Drug: PLX4720
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Sensitive Drug: PLX4720
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Sensitive Drug: PLX4720
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Sensitive Drug: PLX4720
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

PRN1371

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 1 (FGFR1) [80]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V561M (c.1681G>A)
• Sensitive Drug: PRN1371
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [80]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N550K (c.1650T>G)
• Sensitive Drug: PRN1371
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [80]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Sensitive Drug: PRN1371
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [80]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Sensitive Drug: PRN1371
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [80]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650M (c.1949A>T)
• Sensitive Drug: PRN1371
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Pyrotinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• Resistant Drug: Pyrotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• Sensitive Drug: Pyrotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: Pyrotinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

TAK-441

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [81]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D473H (c.1417G>C)
• Sensitive Drug: TAK-441
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: [3H]-TAK-441 radioligand membrane binding assay; Affinity selection-MS binding assay

Discontinued Drug(s) 3 drug(s) in total

Motesanib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [82]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.M552_V559delMYEVQWKV (c.1654_1677del24)
• Sensitive Drug: Motesanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Mechanism Description: The if-deletion p.M552_V559delMYEVQWKV (c.1654_1677del24) in gene KIT cause the sensitivity of Motesanib by aberration of the drug's therapeutic target.

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [82]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y823D (c.2467T>G)
• Sensitive Drug: Motesanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: BRAF kinase assay
• Mechanism Description: The missense mutation p.Y823D (c.2467T>G) in gene KIT cause the sensitivity of Motesanib by aberration of the drug's therapeutic target

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [82]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V560D (c.1679T>A)
• Sensitive Drug: Motesanib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Mechanism Description: The missense mutation p.V560D (c.1679T>A) in gene KIT cause the sensitivity of Motesanib by aberration of the drug's therapeutic target

Tandutinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [83]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.I836delI (c.2508_2510delCAT)
• Sensitive Drug: Tandutinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Celltiter96AQueousOne solution proliferation assay
• Mechanism Description: The if-deletion p.I836delI (c.2508_2510delCAT) in gene FLT3 cause the sensitivity of Tandutinib by aberration of the drug's therapeutic target.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [84]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V559D (c.1676T>A)
• Sensitive Drug: Tandutinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: ELISA assay
• Mechanism Description: The missense mutation p.V559D (c.1676T>A) in gene KIT cause the sensitivity of Tandutinib by unusual activation of pro-survival pathway

AZD-8330

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Resistant Drug: AZD-8330
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Resistant Drug: AZD-8330
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Resistant Drug: AZD-8330
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Resistant Drug: AZD-8330
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Resistant Drug: AZD-8330
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Resistant Drug: AZD-8330
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Drug: AZD-8330
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Preclinical Drug(s) 44 drug(s) in total

A66

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [85]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Resistant Drug: A66
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Skin; .
• In Vivo Model: Mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the resistance of A66 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [85]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Drug: A66
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Skin; .
• In Vivo Model: Mouse xenograft model; Mus musculus
• Mechanism Description: The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of A66 by aberration of the drug's therapeutic target

ACLY siRNA

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: AMP-activated kinase alpha-2 (PRKAA2) [86]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Other; p.T172(Phosphorylation) (c.514_516)
• Sensitive Drug: ACLY siRNA
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The mutation p.T172(Phosphorylation) (c.514_516) in gene PRKAA2 cause the sensitivity of ACLY SiRNA by unusual activation of pro-survival pathway.

AGI-5198/Talazoparib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [36]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Resistant Drug: AGI-5198/Talazoparib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

Allosteric AKT inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-beta serine/threonine-protein kinase (AKT2) [87]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Copy number gain; .
• Sensitive Drug: Allosteric AKT inhibitors
• Experimental Note: Revealed Based on the Cell Line Data

Key Molecule: RAC-beta serine/threonine-protein kinase (AKT2) [87]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Copy number gain; .
• Sensitive Drug: Allosteric AKT inhibitors
• Experimental Note: Revealed Based on the Cell Line Data

ALW-II-41-27

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [88]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C634Y (c.1901G>A)
• Sensitive Drug: ALW-II-41-27
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/V804L cells; N.A.; Mus musculus (Mouse); CVCL_XZ25
• In Vitro Model: RET/S891A cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/L790F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/A883F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: MZ-CRC-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_A656
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell counting assay

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [88]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M918T (c.2753T>C)
• Sensitive Drug: ALW-II-41-27
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/V804L cells; N.A.; Mus musculus (Mouse); CVCL_XZ25
• In Vitro Model: RET/S891A cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/L790F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/A883F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: MZ-CRC-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_A656
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell counting assay

AMGMDS3

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V157F (c.469G>T)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.V157F (c.469G>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R158H (c.473G>A)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R158H (c.473G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R158L (c.473G>T)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R158L (c.473G>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R175H (c.524G>A)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R175H (c.524G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y220C (c.659A>G)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.Y220C (c.659A>G) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G245S (c.733G>A)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.G245S (c.733G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R248W (c.742C>T)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R248W (c.742C>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R248Q (c.743G>A)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R248Q (c.743G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R249S (c.747G>C)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R249S (c.747G>C) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R273C (c.817C>T)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R273C (c.817C>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R273H (c.818G>A)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R273H (c.818G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R280K (c.839G>A)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R280K (c.839G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Key Molecule: Cellular tumor antigen p53 (TP53) [89]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R280T (c.839G>C)
• Resistant Drug: AMGMDS3
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: NCI-H82 cells; Pleural effusion; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Fluorescence microscopy assay
• Mechanism Description: The missense mutation p.R280T (c.839G>C) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway

Anti-HER3 mAbs

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-3 (ERBB3) [90]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G284R (c.850G>A)
• Sensitive Drug: Anti-HER3 mAbs
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.G284R (c.850G>A) in gene ERBB3 cause the sensitivity of anti-HER3 mAbs by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-3 (ERBB3) [90]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.P262H (c.785C>A)
• Sensitive Drug: Anti-HER3 mAbs
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.P262H (c.785C>A) in gene ERBB3 cause the sensitivity of anti-HER3 mAbs by aberration of the drug's therapeutic target

AV-412

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [91]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T790M (c.2369C>T)
• Sensitive Drug: AV-412
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: TE8 cells; Esophageal; Homo sapiens (Human); CVCL_1766
• In Vitro Model: A4 cells; N.A.; Mus musculus (Mouse); CVCL_F962
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: 3H-thymidine incorporation assay
• Mechanism Description: The missense mutation p.T790M (c.2369C>T) in gene EGFR cause the sensitivity of AV-412 by aberration of the drug's therapeutic target

Key Molecule: Epidermal growth factor receptor (EGFR) [91]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: AV-412
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: TE8 cells; Esophageal; Homo sapiens (Human); CVCL_1766
• In Vitro Model: A4 cells; N.A.; Mus musculus (Mouse); CVCL_F962
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: 3H-thymidine incorporation assay
• Mechanism Description: The missense mutation p.L858R (c.2573T>G) in gene EGFR cause the sensitivity of AV-412 by aberration of the drug's therapeutic target

AZ5104

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• Resistant Drug: AZ5104
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)
• Resistant Drug: AZ5104
• Experimental Note: Identified from the Human Clinical Data

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [18]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• Sensitive Drug: AZ5104
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

BEZ235/Ruxolitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Thrombopoietin receptor (TPOR) [92]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W515L (c.1544G>T)
• Sensitive Drug: BEZ235/Ruxolitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: JAK2 mutant Ba/F3 tumour mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Colony assay

Binimetinib/Everolimus

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [6]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q61L (c.182A>T)
• Sensitive Drug: Binimetinib/Everolimus
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: RL952 cells; Endometrium; Homo sapiens (Human); CVCL_0505
• In Vitro Model: NCI-H1915 cells; Lung; Homo sapiens (Human); CVCL_1505
• In Vitro Model: KYSE-30 cells; Esophagus; Homo sapiens (Human); CVCL_1351
• In Vitro Model: KNS62 cells; Brain; Homo sapiens (Human); CVCL_1335
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: HCC44 cells; Lung; Homo sapiens (Human); CVCL_2060
• In Vitro Model: CAL-12T cells; Lung; Homo sapiens (Human); CVCL_1105
• In Vivo Model: CB17 SCID-/- mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

BPR1J373

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [93]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Drug: BPR1J373
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: U937 cells; Blood; Homo sapiens (Human); CVCL_0007
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vivo Model: SCID beige mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: WST1 assay; BD FACSCalibur assay; FACS assay
• Mechanism Description: BPR1J373 inhibits cell proliferation of c-KIT-driven AML cells via induction of apoptosis and cell-cycle arrest.

Cisplatin/Talazoparib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [36]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Sensitive Drug: Cisplatin/Talazoparib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

EAI045

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [94]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: EAI045
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: CellTitre-Glo assay; MTS assay
• Mechanism Description: EAI045 is a kind of EGFR tyrosine kinase inhibitor.

EKI-285

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [95]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: EKI-285
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung adenocarcinomas tissue; .
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.L858R (c.2573T>G) in gene EGFR cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target

Key Molecule: Epidermal growth factor receptor (EGFR) [96]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L844V (c.2530C>G)
• Sensitive Drug: EKI-285
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: HCC827EP cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: H3255DR cells; Lung; Homo sapiens (Human); CVCL_DI56
• In Vitro Model: H197 cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay; CytoSelect 96-well cell transformation assay

Key Molecule: Epidermal growth factor receptor (EGFR) [96]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L718Q (c.2153T>A)
• Sensitive Drug: EKI-285
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: HCC827EP cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: H3255DR cells; Lung; Homo sapiens (Human); CVCL_DI56
• In Vitro Model: H197 cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay; CytoSelect 96-well cell transformation assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T798M (c.2393_2394delCAinsTG)
• Sensitive Drug: EKI-285
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L755S (c.2263_2264delCTinsAG)
• Sensitive Drug: EKI-285
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L755P (c.2264T>C)
• Sensitive Drug: EKI-285
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target

ERBB2 TKIs

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [97]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G309E (c.926G>A)
• Sensitive Drug: ERBB2 TKIs
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: The missense mutation p.G309E (c.926G>A) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [97]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.S310Y (c.929C>A)
• Sensitive Drug: ERBB2 TKIs
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: The missense mutation p.S310Y (c.929C>A) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [97]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.S310F (c.929C>T)
• Sensitive Drug: ERBB2 TKIs
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: The missense mutation p.S310F (c.929C>T) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [97]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C311R (c.931T>C)
• Sensitive Drug: ERBB2 TKIs
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: The missense mutation p.C311R (c.931T>C) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [97]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E321G (c.962A>G)
• Sensitive Drug: ERBB2 TKIs
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: The missense mutation p.E321G (c.962A>G) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target

FIIN-1

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 1 (FGFR1) [98]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V561M (c.1681G>A)
• Sensitive Drug: FIIN-1
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Drug Resistance: CellTiter-Glo Luminescent Cell Viability Assay
• Mechanism Description: The missense mutation p.V561M (c.1681G>A) in gene FGFR1 cause the sensitivity of FIIN-1 by aberration of the drug's therapeutic target

FIIN-2

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N540K (c.1620C>G)
• Resistant Drug: FIIN-2
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.N540K (c.1620C>G) in gene FGFR3 cause the resistance of FIIN-2 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V555M (c.1663G>A)
• Resistant Drug: FIIN-2
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.V555M (c.1663G>A) in gene FGFR3 cause the resistance of FIIN-2 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Sensitive Drug: FIIN-2
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of FIIN-2 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [23]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L608V (c.1822T>G)
• Sensitive Drug: FIIN-2
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Gallbladder; .
• Experiment for Molecule Alteration: Targeted sequencing of tumor tissue assay
• Mechanism Description: The missense mutation p.L608V (c.1822T>G) in gene FGFR3 cause the sensitivity of FIIN-2 by aberration of the drug's therapeutic target

GDC0879

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Resistant Drug: GDC0879
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Resistant Drug: GDC0879
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Resistant Drug: GDC0879
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Resistant Drug: GDC0879
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Resistant Drug: GDC0879
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Resistant Drug: GDC0879
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Drug: GDC0879
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Glesatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1003F (c.3008A>T)
• Sensitive Drug: Glesatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Hepatocyte growth factor receptor (MET) [11]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1010Y (c.3028G>T)
• Sensitive Drug: Glesatinib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vitro Model: Gp2-293 cells; Fetal kidney; Homo sapiens (Human); CVCL_WI48
• Experiment for Molecule Alteration: Direct sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Hepatocyte growth factor receptor (MET) [13]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228V (c.3683A>T)
• Sensitive Drug: Glesatinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: There is a patient with metastatic NSCLC with MET-mediated resistance to EGFR TKI who responded to treatment with a type I MET inhibitor, savolitinib, given in combination with a third-generation EGFR inhibitor, osimertinib. The patient then developed acquired resistance mediated by a novel MET kinase domain mutation.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Hepatocyte growth factor receptor (MET) [99]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230C (c.3689A>G)
• Sensitive Drug: Glesatinib
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MET signaling pathway; Inhibition; hsa04150
• In Vitro Model: NCI-H441 cells; Lung; Homo sapiens (Human); CVCL_1561
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: NCI-H596 cells; Lung; Homo sapiens (Human); CVCL_1571
• In Vitro Model: Hs746T cells; Skeletal muscle; Homo sapiens (Human); CVCL_0333
• In Vivo Model: Nu/Nu mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis

HG-6-63-01

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [88]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C634Y (c.1901G>A)
• Sensitive Drug: HG-6-63-01
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/V804L cells; N.A.; Mus musculus (Mouse); CVCL_XZ25
• In Vitro Model: RET/S891A cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/L790F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/A883F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: MZ-CRC-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_A656
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell counting assay

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [88]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M918T (c.2753T>C)
• Sensitive Drug: HG-6-63-01
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/V804L cells; N.A.; Mus musculus (Mouse); CVCL_XZ25
• In Vitro Model: RET/S891A cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/L790F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/A883F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: MZ-CRC-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_A656
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell counting assay

HSP90 inhibitor

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [59]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R248Q (c.743G>A)
• Sensitive Drug: HSP90 inhibitor
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-46 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vitro Model: EFO21 cells; Ascites; Homo sapiens (Human); CVCL_0029
• In Vitro Model: COV434 cells; N.A.; Homo sapiens (Human); CVCL_2010
• In Vitro Model: COLO704 cells; Ascites; Homo sapiens (Human); CVCL_1994
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vivo Model: Athymic (nu/nu) male xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Quantitative PCR analysis
• Experiment for Drug Resistance: CellTiter-blue cell viability assay

Key Molecule: Cellular tumor antigen p53 (TP53) [59]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R175H (c.524G>A)
• Sensitive Drug: HSP90 inhibitor
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ES2 cells; Ovary; Homo sapiens (Human); CVCL_AX39
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-46 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vitro Model: EFO21 cells; Ascites; Homo sapiens (Human); CVCL_0029
• In Vitro Model: COV434 cells; N.A.; Homo sapiens (Human); CVCL_2010
• In Vitro Model: COLO704 cells; Ascites; Homo sapiens (Human); CVCL_1994
• In Vitro Model: HOC7 cells; Ascites; Homo sapiens (Human); CVCL_5455
• In Vivo Model: Athymic (nu/nu) male xenograft mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Quantitative PCR analysis
• Experiment for Drug Resistance: CellTiter-blue cell viability assay

Ibrutinib/Ruxolitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [100]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Nonsense; p.Q741* (c.2221C>T)
• Sensitive Drug: Ibrutinib/Ruxolitinib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: BTK signaling pathway; Inhibition; hsa04662
• Experiment for Drug Resistance: Trypan blue staining assay
• Mechanism Description: G-CSFR mutants showed abnormal kinetics of canonical STAT3, STAT5 and MAPK phosphorylation, and aberrant activation of Bruton's Tyrosine Kinase (Btk).

Key Molecule: Granulocyte colony-stimulating factor receptor (CSF3R) [100]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T618I (c.1853C>T)
• Sensitive Drug: Ibrutinib/Ruxolitinib
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: BTK signaling pathway; Inhibition; hsa04662
• Experiment for Drug Resistance: Trypan blue staining assay
• Mechanism Description: G-CSFR mutants showed abnormal kinetics of canonical STAT3, STAT5 and MAPK phosphorylation, and aberrant activation of Bruton's Tyrosine Kinase (Btk).

JBJ-04-125-02

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [101]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-deletion; p.E746_A750delELREA (c.2236_2250del15)
• Resistant Drug: JBJ-04-125-02
• Experimental Note: Identified from the Human Clinical Data

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [101]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: JBJ-04-125-02
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vivo Model: Genetically engineered mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: MTS assay

JQ1/Osimertinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [102]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.Y772_A775dupYVMA (c.2325_2326insTATGTAATGGCA)
• Sensitive Drug: JQ1/Osimertinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NCI-H1781 cells; Pleural effusion; Homo sapiens (Human); CVCL_1494
• Experiment for Molecule Alteration: Western blotting analysis; Immunohistochemistry; H&E staining assay
• Experiment for Drug Resistance: CCK-8 assay

MK2206

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [103]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W80A (c.238_239delTGinsGC)
• Resistant Drug: MK2206
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 3T3-L1 cells; Nasopharynx; Mus musculus (Mouse); CVCL_0123
• Mechanism Description: The missense mutation p.W80A (c.238_239delTGinsGC) in gene AKT1 cause the resistance of MK2206 by aberration of the drug's therapeutic target

MRK-003

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [104]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.A1707T (c.5119G>A)
• Sensitive Drug: MRK-003
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-157 cells; Breast; Homo sapiens (Human); CVCL_0618
• In Vitro Model: TNsBC cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: T-ALL cells; Bone marrow; Homo sapiens (Human); CVCL_1736
• In Vitro Model: HCC2218 cells; Breast; Homo sapiens (Human); CVCL_1263
• In Vitro Model: HCC1187 cells; Breast; Homo sapiens (Human); CVCL_1247
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer-Glo luminescent assay; Luciferase assay

MRT-92

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [105]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V329F (c.985_987delGTGinsTTT)
• Resistant Drug: MRT-92
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [105]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D384A (c.1151A>C)
• Resistant Drug: MRT-92
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [105]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y394A (c.1180_1181delTAinsGC)
• Resistant Drug: MRT-92
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [105]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T466F (c.1396_1397delACinsTT)
• Resistant Drug: MRT-92
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [105]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E518K (c.1552G>A)
• Resistant Drug: MRT-92
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [105]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M525G (c.1573_1574delATinsGG)
• Resistant Drug: MRT-92
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [105]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L325F (c.973_975delCTGinsTTT)
• Resistant Drug: MRT-92
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [105]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R400A (c.1198_1199delCGinsGC)
• Sensitive Drug: MRT-92
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

NIBR3049

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [37]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V674A (c.2021T>C)
• Resistant Drug: NIBR3049
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [37]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L857P (c.2570T>C)
• Sensitive Drug: NIBR3049
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: U4C cells; Acetabulum; Homo sapiens (Human); CVCL_D314
• In Vivo Model: Balb/c bone marrow transplantation mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Proliferation assay

OBX1-012

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Epidermal growth factor receptor (EGFR) [106]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.P772_H773insGNP (c.2316_2317insGGTAACCCT)
• Resistant Drug: OBX1-012
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: OBX1-012 treatment was highly effective against human EGFR-mutant lung cancer models with or without EGFR T790M, not only in vitro but also in vivo. However, OBX1-012 like other EGFR-TKIs failed to exhibit efficacy for the exon 20 insertion mutation or C797S mutation, which was generated by site-directed mutagenesis and stable transfection of Ba/F3 cells.

PARP inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [36]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Sensitive Drug: PARP inhibitors
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

PI3K pathway inhibitors/MEK inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-3 (ERBB3) [90]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q809R (c.2426A>G)
• Sensitive Drug: PI3K pathway inhibitors/MEK inhibitors
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.Q809R (c.2426A>G) in gene ERBB3 cause the sensitivity of PI3K pathway inhibitors + MEK inhibitors by unusual activation of pro-survival pathway

Key Molecule: Receptor tyrosine-protein kinase erbB-3 (ERBB3) [90]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.P262H (c.785C>A)
• Sensitive Drug: PI3K pathway inhibitors/MEK inhibitors
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.P262H (c.785C>A) in gene ERBB3 cause the sensitivity of PI3K pathway inhibitors + MEK inhibitors by unusual activation of pro-survival pathway

Key Molecule: Receptor tyrosine-protein kinase erbB-3 (ERBB3) [90]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G284R (c.850G>A)
• Sensitive Drug: PI3K pathway inhibitors/MEK inhibitors
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.G284R (c.850G>A) in gene ERBB3 cause the sensitivity of PI3K pathway inhibitors + MEK inhibitors by unusual activation of pro-survival pathway

Key Molecule: Receptor tyrosine-protein kinase erbB-3 (ERBB3) [90]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q809R (c.2426A>G)
• Sensitive Drug: PI3K pathway inhibitors/MEK inhibitors
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.Q809R (c.2426A>G) in gene ERBB3 cause the sensitivity of PI3K pathway inhibitors + MEK inhibitors by unusual activation of pro-survival pathway

Key Molecule: Receptor tyrosine-protein kinase erbB-3 (ERBB3) [90]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.P262H (c.785C>A)
• Sensitive Drug: PI3K pathway inhibitors/MEK inhibitors
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.P262H (c.785C>A) in gene ERBB3 cause the sensitivity of PI3K pathway inhibitors + MEK inhibitors by unusual activation of pro-survival pathway

Key Molecule: Receptor tyrosine-protein kinase erbB-3 (ERBB3) [90]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G284R (c.850G>A)
• Sensitive Drug: PI3K pathway inhibitors/MEK inhibitors
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.G284R (c.850G>A) in gene ERBB3 cause the sensitivity of PI3K pathway inhibitors + MEK inhibitors by unusual activation of pro-survival pathway

Pictilisib/Ruxolitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [92]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V617F (c.1849G>T)
• Sensitive Drug: Pictilisib/Ruxolitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: JAK2 mutant Ba/F3 tumour mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Colony assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Thrombopoietin receptor (TPOR) [92]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.W515L (c.1544G>T)
• Sensitive Drug: Pictilisib/Ruxolitinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: JAK2 mutant Ba/F3 tumour mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Colony assay

PZ-1

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [107]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V804M (c.2410G>A)
• Sensitive Drug: PZ-1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Microfluidic separation based assay

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [107]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V804L (c.2410G>C)
• Sensitive Drug: PZ-1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Microfluidic separation based assay

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [107]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M918T (c.2753T>C)
• Sensitive Drug: PZ-1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Microfluidic separation based assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [107]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G12V (c.35G>T)
• Sensitive Drug: PZ-1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vivo Model: Nu/Nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Microfluidic separation based assay

R3Mab

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [108]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.S249C (c.746C>G)
• Sensitive Drug: R3Mab
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.S249C (c.746C>G) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [108]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G372C (c.1114G>T)
• Sensitive Drug: R3Mab
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.G372C (c.1114G>T) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [108]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y375C (c.1124A>G)
• Sensitive Drug: R3Mab
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.Y375C (c.1124A>G) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [108]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K652E (c.1954A>G)
• Sensitive Drug: R3Mab
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.K652E (c.1954A>G) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [108]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R248C (c.742C>T)
• Sensitive Drug: R3Mab
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: KMS11 cells; Peripheral blood; Homo sapiens (Human); CVCL_2989
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: UTMC-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_4802
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: TCC-97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Mechanism Description: The missense mutation p.R248C (c.742C>T) in gene FGFR3 cause the sensitivity of R3Mab by aberration of the drug's therapeutic target

ReACp53

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [109]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R175H (c.524G>A)
• Sensitive Drug: ReACp53
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: S1 GODL cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Immunocompromised NSG mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: In vitro 3D organoid assay

Ruxolitinib/ZSTK474

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [92]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V617F (c.1849G>T)
• Sensitive Drug: Ruxolitinib/ZSTK474
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: JAK2 mutant Ba/F3 tumour mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Colony assay

SB590885

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [70]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: SB590885
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: BRAF kinase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of SB590885 by aberration of the drug's therapeutic target

Spliceosome inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Splicing factor 3B subunit 1 (SF3B1) [110]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K700E (c.2098A>G)
• Sensitive Drug: Spliceosome inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: Panc 0504 cells; Pancreas; Homo sapiens (Human); CVCL_1637
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: HEC59 cells; Endometrium; Homo sapiens (Human); CVCL_2930
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Splicing factor 3B subunit 1 (SF3B1) [110]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K666N (c.1998G>C)
• Sensitive Drug: Spliceosome inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Capan-1 cells; Pancreas; Homo sapiens (Human); CVCL_0237
• In Vitro Model: Capan-2 cells; Pancreas; Homo sapiens (Human); CVCL_0026
• In Vitro Model: HEC1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vitro Model: Panc 0504 cells; Pancreas; Homo sapiens (Human); CVCL_1637
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: HEC59 cells; Endometrium; Homo sapiens (Human); CVCL_2930
• In Vitro Model: ESS-1 cells; Endometrium; Homo sapiens (Human); CVCL_1205
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

SR-9009

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [111]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G12V (c.35G>T)
• Sensitive Drug: SR-9009
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: Sk-Mel28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: WI38 cells; Fetal lung; Homo sapiens (Human); CVCL_0579
• In Vitro Model: BJ-ELR cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: BJ cells; Peripheral blood; Homo sapiens (Human); CVCL_E483
• In Vitro Model: Becker cells; N.A.; Homo sapiens (Human); CVCL_1093
• In Vivo Model: NOD mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunofluorescence microscopy assay; qRT-PCR
• Mechanism Description: Pharmacological modulation of circadian regulators is an effective novel antitumor strategy, identifying the existence of a previously unknown class of anticancer agents with a wide therapeutic window. REV-ERB agonists are novel autophagy and de novo lipogenesis inhibitors with selective activity towards malignant and benign neoplasms.

TAE226

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Epidermal growth factor receptor (EGFR) [112]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Drug: TAE226
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H2228 cells; Lung; Homo sapiens (Human); CVCL_1543
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H838 cells; Lung; Homo sapiens (Human); CVCL_1594
• In Vitro Model: NCI-H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: HCC4006 cells; Lung; Homo sapiens (Human); CVCL_1269
• In Vitro Model: NCI-H1395 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: NCI-H820 cells; Lymph node; Homo sapiens (Human); CVCL_1592
• In Vitro Model: NCI-H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: NCI-H1993 cells; Lymph node; Homo sapiens (Human); CVCL_1512
• In Vitro Model: NCI-H1819 cells; Lymph node; Homo sapiens (Human); CVCL_1497
• In Vitro Model: NCI-H1666 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: NCI-H1648 cells; Lymph node; Homo sapiens (Human); CVCL_1482
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: MKN45 cells; Liver; Homo sapiens (Human); CVCL_0434
• In Vivo Model: BALB/c-nu/nu female nude mouse PC9 xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-96 AQueous One assay

TAS6417

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [113]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.A763_Y764insFQEA (c.2290_2291insTTCAAGAGGCAT)
• Sensitive Drug: TAS6417
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: NCI-H1875 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: LXF 2378L cells; N.A.; .; N.A.
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations.

Key Molecule: Epidermal growth factor receptor (EGFR) [113]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.A767_V769 (c.2299_2307)
• Sensitive Drug: TAS6417
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: NCI-H1875 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: LXF 2378L cells; N.A.; .; N.A.
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations.

Key Molecule: Epidermal growth factor receptor (EGFR) [113]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Sensitive Drug: TAS6417
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: NCI-H1875 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: LXF 2378L cells; N.A.; .; N.A.
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations.

Key Molecule: Epidermal growth factor receptor (EGFR) [113]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: IF-insertion; p.D770_N771insG (c.2310_2311insGGT)
• Sensitive Drug: TAS6417
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: NCI-H1875 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: LXF 2378L cells; N.A.; .; N.A.
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations.

Key Molecule: Epidermal growth factor receptor (EGFR) [113]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.N771_H773 (c.2311_2319)
• Sensitive Drug: TAS6417
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: NCI-H1875 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: LXF 2378L cells; N.A.; .; N.A.
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations.

Key Molecule: Epidermal growth factor receptor (EGFR) [113]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Duplication; p.P772_H773 (c.2314_2319)
• Sensitive Drug: TAS6417
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• In Vitro Model: NCI-H1875 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: LXF 2378L cells; N.A.; .; N.A.
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations.

WZ4002

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L755S (c.2263_2264delCTinsAG)
• Sensitive Drug: WZ4002
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the sensitivity of WZ4002 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L755P (c.2264T>C)
• Sensitive Drug: WZ4002
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the sensitivity of WZ4002 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [74]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.T798M (c.2393_2394delCAinsTG)
• Sensitive Drug: WZ4002
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of WZ4002 by aberration of the drug's therapeutic target

XMD15-44

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [88]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C634Y (c.1901G>A)
• Sensitive Drug: XMD15-44
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/V804L cells; N.A.; Mus musculus (Mouse); CVCL_XZ25
• In Vitro Model: RET/S891A cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/L790F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/A883F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: MZ-CRC-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_A656
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell counting assay

Key Molecule: Proto-oncogene tyrosine-protein kinase receptor Ret (RET) [88]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M918T (c.2753T>C)
• Sensitive Drug: XMD15-44
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: TT cells; Thyroid gland; Homo sapiens (Human); CVCL_1774
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/V804L cells; N.A.; Mus musculus (Mouse); CVCL_XZ25
• In Vitro Model: RET/S891A cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/M918T cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/L790F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/C634R cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: RET/A883F cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: MZ-CRC-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_A656
• In Vitro Model: RET/V804M cells; Bone marrow; Mus musculus (Mouse); CVCL_XZ26
• In Vitro Model: RET/E768D cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell counting assay

Investigative Drug(s) 14 drug(s) in total

CI-1040

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [114]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I103N (c.308T>A)
• Resistant Drug: CI-1040
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain SY2002; 4932
• Experiment for Molecule Alteration: Kinase assay
• Mechanism Description: The missense mutation p.I103N (c.308T>A) in gene MAP2K1 cause the resistance of CI-1040 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [114]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L115A (c.343_344delCTinsGC)
• Resistant Drug: CI-1040
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain SY2002; 4932
• Experiment for Molecule Alteration: Kinase assay
• Mechanism Description: The missense mutation p.L115A (c.343_344delCTinsGC) in gene MAP2K1 cause the resistance of CI-1040 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [114]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L115P (c.344T>C)
• Resistant Drug: CI-1040
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain SY2002; 4932
• Experiment for Molecule Alteration: Kinase assay
• Mechanism Description: The missense mutation p.L115P (c.344T>C) in gene MAP2K1 cause the resistance of CI-1040 by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [70]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: CI-1040
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: BRAF kinase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of CI-1040 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [114]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F53S (c.158T>C)
• Sensitive Drug: CI-1040
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain SY2002; 4932
• Experiment for Molecule Alteration: Kinase assay
• Mechanism Description: The missense mutation p.F53S (c.158T>C) in gene MAP2K1 cause the sensitivity of CI-1040 by unusual activation of pro-survival pathway

ERK inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Nras (NRAS) [115]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G12C (c.34G>T)
• Sensitive Drug: ERK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Fluorescence-activated cell sorting assay
• Mechanism Description: The missense mutation p.G12C (c.34G>T) in gene NRAS cause the sensitivity of ERK inhibitors by unusual activation of pro-survival pathway

Formononetin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Ewing sarcoma associated transcript 1 (EWSAT1) [116]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Up-regulation; Expression
• Resistant Drug: Formononetin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: human umbilical vein endothelial cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female SD rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Microarray assay; qRT-PCR; Western bloting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Formononetin, J1 and J2 have different effects on endothelial cells via EWSAT1-TRAF6 and its downstream pathway.

Futuximab

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Epidermal growth factor receptor (EGFR) [117]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R451C (c.1351C>T)
• Sensitive Drug: Futuximab
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Regulation; hsa01521
• In Vitro Model: LIM1215 cells; Colon; Homo sapiens (Human); CVCL_2574
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EGFR cells; N.A.; .; N.A.
• In Vivo Model: Male BALB/c nude mouse; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay; FACS assay; Crystal violet staining assay
• Mechanism Description: Contrary to cetuximab and panitumumab, Sym004 effectively binds to and prevents activation of all the EGFR mutants. Sym004 effectively inhibits proliferation and EGFR downstream signaling in cetuximab-resistant derivatives harboring the S492R and G465R EGFR mutations. Sym004 causes profound and sustained regression in S492R-mutant EGFR and delays tumor growth in G465R-mutant EGFR in vivo.

Key Molecule: Epidermal growth factor receptor (EGFR) [117]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K467T (c.1400A>C)
• Sensitive Drug: Futuximab
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Regulation; hsa01521
• In Vitro Model: LIM1215 cells; Colon; Homo sapiens (Human); CVCL_2574
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EGFR cells; N.A.; .; N.A.
• In Vivo Model: Male BALB/c nude mouse; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay; FACS assay; Crystal violet staining assay
• Mechanism Description: Contrary to cetuximab and panitumumab, Sym004 effectively binds to and prevents activation of all the EGFR mutants. Sym004 effectively inhibits proliferation and EGFR downstream signaling in cetuximab-resistant derivatives harboring the S492R and G465R EGFR mutations. Sym004 causes profound and sustained regression in S492R-mutant EGFR and delays tumor growth in G465R-mutant EGFR in vivo.

JANEX-1

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [118]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I87T (c.260T>C)
• Sensitive Drug: JANEX-1
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.I87T (c.260T>C) in gene JAK3 cause the sensitivity of JANEX-1 by aberration of the drug's therapeutic target

MEK inhibitors

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D67N (c.199G>A)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.D67N (c.199G>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I99T (c.296T>C)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.I99T (c.296T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I103N (c.308T>A)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.I103N (c.308T>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K104N (c.312A>C)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.K104N (c.312A>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I111N (c.332T>A)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.I111N (c.332T>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L115P (c.344T>C)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.L115P (c.344T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H119P (c.356A>C)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.H119P (c.356A>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E120D (c.360G>C)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.E120D (c.360G>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G128D (c.383G>A)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.G128D (c.383G>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F133L (c.397T>C)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.F133L (c.397T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [119]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L215P (c.644T>C)
• Resistant Drug: MEK inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.L215P (c.644T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

MET inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [120]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H1112L (c.3335A>T)
• Sensitive Drug: MET inhibitors
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.

N-arachidonoyl dopamine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Nras (NRAS) [121]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.G12D (c.35G>A)
• Sensitive Drug: N-arachidonoyl dopamine
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: WEHI-3 cells; Peripheral blood; Mus musculus (Mouse); CVCL_3622
• In Vitro Model: Bosc23 cells; Fetal kidney; Homo sapiens (Human); CVCL_4401
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation.

Non-allosteric AKT inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [122]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Drug: Non-allosteric AKT inhibitors
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of non-allosteric AKT inhibitors by aberration of the drug's therapeutic target

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [122]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Drug: Non-allosteric AKT inhibitors
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [122]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E17K (c.49G>A)
• Sensitive Drug: Non-allosteric AKT inhibitors
• Experimental Note: Identified from the Human Clinical Data

PD-180970

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [84]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V559D (c.1676T>A)
• Sensitive Drug: PD-180970
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: ELISA assay
• Mechanism Description: The missense mutation p.V559D (c.1676T>A) in gene KIT cause the sensitivity of PD-180970 by unusual activation of pro-survival pathway

PD173074

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.K660E (c.1978A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M536I (c.1608G>C)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.M536I (c.1608G>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M538I (c.1614G>C)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.M538I (c.1614G>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I548V (c.1642A>G)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.I548V (c.1642A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N550H (c.1648A>C)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550H (c.1648A>C) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N550S (c.1649A>G)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550S (c.1649A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N550K (c.1650T>G)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.N550K (c.1650T>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V565I (c.1693G>A)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.V565I (c.1693G>A) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E566G (c.1697A>G)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.E566G (c.1697A>G) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [123]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L618M (c.1852T>A)
• Resistant Drug: PD173074
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: In vitro kinase inhibition assay
• Mechanism Description: The missense mutation p.L618M (c.1852T>A) in gene FGFR2 cause the resistance of PD173074 by aberration of the drug's therapeutic target

PD98059

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Resistant Drug: PD98059
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Resistant Drug: PD98059
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Resistant Drug: PD98059
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Resistant Drug: PD98059
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Resistant Drug: PD98059
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Resistant Drug: PD98059
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [35]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Drug: PD98059
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [124]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.K650E (c.1948A>G)
• Sensitive Drug: PD98059
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: COS-1 cells; Kidney; Chlorocebus aethiops (Green monkey); CVCL_0223
• Experiment for Molecule Alteration: Immunoprecipitation and immunoblot analysis
• Mechanism Description: The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of PD98059 by unusual activation of pro-survival pathway

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [28]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R834Q (c.2501G>A)
• Sensitive Drug: PD98059
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bone marrow; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.R834Q (c.2501G>A) in gene FLT3 cause the sensitivity of PD98059 by aberration of the drug's therapeutic target

Pyridone 6

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [125]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R201L (c.602G>T)
• Sensitive Drug: Pyridone 6
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human liver cancer tissue; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.R201L (c.602G>T) in gene GNAS cause the sensitivity of JAK inhibitors by unusual activation of pro-survival pathway

Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) [125]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.R201H (c.602G>A)
• Sensitive Drug: Pyridone 6
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human liver cancer tissue; .
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.R201H (c.602G>A) in gene GNAS cause the sensitivity of JAK inhibitors by unusual activation of pro-survival pathway

SU11274

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [126]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.N375S (c.1124A>G)
• Resistant Drug: SU11274
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; .
• Mechanism Description: The missense mutation p.N375S (c.1124A>G) in gene MET cause the resistance of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [127]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.L1213V (c.3637C>G)
• Resistant Drug: SU11274
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.L1213V (c.3637C>G) in gene MET cause the resistance of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [127]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1248H (c.3742T>C)
• Resistant Drug: SU11274
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.Y1248H (c.3742T>C) in gene MET cause the resistance of SU11274 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [127]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.M1268T (c.3803T>C)
• Sensitive Drug: SU11274
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.M1268T (c.3803T>C) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [128]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V1110I (c.3328G>A)
• Sensitive Drug: SU11274
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V1110I (c.3328G>A) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [128]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H1112L (c.3335A>T)
• Sensitive Drug: SU11274
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.H1112L (c.3335A>T) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [128]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V1206L (c.3616G>C)
• Sensitive Drug: SU11274
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V1206L (c.3616G>C) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [128]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.V1238I (c.3712G>A)
• Sensitive Drug: SU11274
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V1238I (c.3712G>A) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [126]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.E168D (c.504G>C)
• Sensitive Drug: SU11274
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; .
• Mechanism Description: The missense mutation p.E168D (c.504G>C) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [127]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.H1112Y (c.3334C>T)
• Sensitive Drug: SU11274
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.H1112Y (c.3334C>T) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

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