Drug Information

Drug (ID: DG00677) and It's Reported Resistant Information

• Name: Trametinib
• Synonyms: Trametinib; 871700-17-3; GSK1120212; Mekinist; GSK-1120212; JTP 74057; JTP-74057; GSK 1120212; Trametinib (GSK1120212); N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]acetamide; GSK212; UNII-33E86K87QN; TMT212; CHEBI:75998; TMT-212; 33E86K87QN; N-(3-{3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)acetamide; N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide; N-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide; Trametinib [USAN:INN]; trametinibum; JTP74057; N-(3-(3-Cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7- tetrahydropyrido(4,3-d)pyrimidin-1(2H)-yl)phenyl)acetamide; N-(3-{3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7- tetrahydropyrido(4,3-d)pyrimidin-1(2H)-yl}phenyl)acetamide; QOM; Trametinib (USAN); Trametinib (GSK1120212JTP 74057); SCHEMBL170938; C26H23FIN5O4; GTPL6495; QCR-39; GSK1120212 (Trametinib); CHEMBL2103875; EX-A022; BCPP000218; DTXSID901007381; HMS3295I05; HMS3656J11; AOB87707; BCP02307; BDBM50531540; MFCD17215075; NSC758246; NSC800956; s2673; ZINC43100709; AKOS015850628; AM90271; CCG-264976; CS-0060; DB08911; EX-5957; NSC-758246; NSC-800956; SB16553; NCGC00263180-01; NCGC00263180-07; NCGC00263180-14; AC-25891; AS-19382; HY-10999; N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodo-anilino)-6,8-dimethyl-2,4,7-trioxo-pyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide; FT-0688438; SW218089-2; X7454; A25168; D10175; GSK1120212 - JTP-74057; GSK1120212,JTP-74057, GSK212; SR-01000941589; A1-01871; J-523325; Q7833138; SR-01000941589-1; BRD-K12343256-001-01-4; Acetamide, N-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-3,4,6,7-tetrahydro-6,8- dimethyl-2,4,7-trioxopyrido(4,3-d)pyrimidin-1(2H)-yl)phenyl)-; Acetamide, N-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]-; N-(3-(3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide; N-[3-[3-Cyclopropyl-5-[(2-Fluoro-4-Iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2h)-yl]phe nyl]acetamide; N-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxopyrido[3,4-e]pyrimidin-1-yl]phenyl]acetamide; N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}ethanimidic acid; N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide
• Indication:
  In total 1 Indication(s)
  Melanoma [ICD-11: 2C30]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Melanoma [ICD-11: 2C30]; [2]
  Neurofibromatoses [ICD-11: LD2D]; [3]
  Pancreatic cancer [ICD-11: 2C10]; [4]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Head and neck cancer [ICD-11: 2D42]; [1]
• Target: MAPK/ERK kinase kinase (MAP3K); NOUNIPROTAC; [1]
• Formula: C26H23FIN5O4
• IsoSMILES: CC1=C2C(=C(N(C1=O)C)NC3=C(C=C(C=C3)I)F)C(=O)N(C(=O)N2C4=CC=CC(=C4)NC(=O)C)C5CC5
• InChI: 1S/C26H23FIN5O4/c1-13-22-21(23(31(3)24(13)35)30-20-10-7-15(28)11-19(20)27)25(36)33(17-8-9-17)26(37)32(22)18-6-4-5-16(12-18)29-14(2)34/h4-7,10-12,17,30H,8-9H2,1-3H3,(H,29,34)
• InChIKey: LIRYPHYGHXZJBZ-UHFFFAOYSA-N
• PubChem CID: 11707110
• ChEBI ID: CHEBI:75998
• TTD Drug ID: D04XVN
• DrugBank ID: DB08911

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [6]

• Molecule Alteration: Missense mutation; p.F247L (c.739T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [7]

• Molecule Alteration: Missense mutation; p.Y288C (c.863A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [8]

• Molecule Alteration: Missense mutation; p.L597S (c.1789_1790delCTinsTC)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Melanoma thyroid metastasis; N.A.
• 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) [8]

• Molecule Alteration: Missense mutation; p.L597R (c.1790T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Melanoma thyroid metastasis; N.A.
• 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) [8]

• Molecule Alteration: Missense mutation; p.K601E (c.1801A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Melanoma thyroid metastasis; N.A.
• 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) [9]

• Molecule Alteration: Missense mutation; p.N610S (c.1829A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [9]

• Molecule Alteration: Missense mutation; p.N610H (c.1828A>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [10]

• Molecule Alteration: Missense mutation; p.N345K (c.1035T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [10]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [10]

• Molecule Alteration: Missense mutation; p.Q546K (c.1636C>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [10]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [10]

• Molecule Alteration: Missense mutation; p.G1049R (c.3145G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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

Atypical chronic myeloid leukemia [ICD-11: 2A41]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein kinase C eta type (PRKCH) [11]

• Molecule Alteration: Copy number gain; .
• Sensitive Disease: Atypical chronic myeloid leukemia [ICD-11: 2A41.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human CML cells; Peripheral blood; Homo sapiens (Human); CVCL_E508
• In Vitro Model: BCR-ABL mouse primary bone marrow cells; N.A.; Mus musculus (Mouse); N.A.
• In Vivo Model: Mouse model of BCR-ABL-independent IM-resistant CML; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assay

Gastric cancer [ICD-11: 2B72]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• 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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• 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: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• 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: 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: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• 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) [12]

• Molecule Alteration: Missense mutation; p.G466V (c.1397G>T)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK signaling pathway; Activation; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: H1650 cells; Pleural effusion; Homo sapiens (Human); CVCL_4V01
• In Vitro Model: HTB-56 cells; Pleural effusion; Homo sapiens (Human); CVCL_0236
• In Vitro Model: HTB-38 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HTB-183 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H661 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H508 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: H2405 cells; Lung; Homo sapiens (Human); CVCL_1551
• In Vitro Model: H1666 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: H1395 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: CRL-5944 cells; Ascites; Homo sapiens (Human); CVCL_1551
• In Vitro Model: CRL-5885 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: CRL-5883 cells; Pleural effusion; Homo sapiens (Human); CVCL_1483
• In Vitro Model: CRL-5868 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: CRL-5803 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: CCL-253 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: CCL-185 cells; Bowel; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Calu-6 cells; Lung; Homo sapiens (Human); CVCL_0236
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Researchers defined three distinct functional classes of BRAF mutants in human tumours. The mutants activate ERK signalling by different mechanisms that dictate their sensitivity to therapeutic inhibitors of the pathway.

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [12]

• Molecule Alteration: Missense mutation; p.G596R (c.1786G>C)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK signaling pathway; Activation; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: H1650 cells; Pleural effusion; Homo sapiens (Human); CVCL_4V01
• In Vitro Model: HTB-56 cells; Pleural effusion; Homo sapiens (Human); CVCL_0236
• In Vitro Model: HTB-38 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HTB-183 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H661 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H508 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: H2405 cells; Lung; Homo sapiens (Human); CVCL_1551
• In Vitro Model: H1666 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: H1395 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: CRL-5944 cells; Ascites; Homo sapiens (Human); CVCL_1551
• In Vitro Model: CRL-5885 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: CRL-5883 cells; Pleural effusion; Homo sapiens (Human); CVCL_1483
• In Vitro Model: CRL-5868 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: CRL-5803 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: CCL-253 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: CCL-185 cells; Bowel; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Calu-6 cells; Lung; Homo sapiens (Human); CVCL_0236
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Researchers defined three distinct functional classes of BRAF mutants in human tumours. The mutants activate ERK signalling by different mechanisms that dictate their sensitivity to therapeutic inhibitors of the pathway.

Pancreatic cancer [ICD-11: 2C10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [4]

• Molecule Alteration: Missense mutation; p.K601E (c.1801A>G)
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: NT-3 cells; Lymph node; Homo sapiens (Human); CVCL_VG81
• Experiment for Drug Resistance: BioRad TC20 automated cell counter 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) [13]

• Molecule Alteration: Complex-indel; p.V487_P492delinsA (c.1460_1474del15)
• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• 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

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [14]

• Molecule Alteration: IF-deletion; p.N486_P490delNVTAP (c.1457_1471del15)
• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood sample; N.A.

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• 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) [12]

• Molecule Alteration: Missense mutation; p.G466V (c.1397G>T)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK signaling pathway; Activation; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: H1650 cells; Pleural effusion; Homo sapiens (Human); CVCL_4V01
• In Vitro Model: HTB-56 cells; Pleural effusion; Homo sapiens (Human); CVCL_0236
• In Vitro Model: HTB-38 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HTB-183 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H661 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H508 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: H2405 cells; Lung; Homo sapiens (Human); CVCL_1551
• In Vitro Model: H1666 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: H1395 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: CRL-5944 cells; Ascites; Homo sapiens (Human); CVCL_1551
• In Vitro Model: CRL-5885 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: CRL-5883 cells; Pleural effusion; Homo sapiens (Human); CVCL_1483
• In Vitro Model: CRL-5868 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: CRL-5803 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: CCL-253 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: CCL-185 cells; Bowel; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Calu-6 cells; Lung; Homo sapiens (Human); CVCL_0236
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Researchers defined three distinct functional classes of BRAF mutants in human tumours. The mutants activate ERK signalling by different mechanisms that dictate their sensitivity to therapeutic inhibitors of the pathway.

Key Molecule: Serine/threonine-protein kinase A-Raf (ARAF) [15]

• Molecule Alteration: Missense mutation; p.S214C (c.641C>G)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: AALE cells; N.A.; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta); CVCL_Z230
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Soft-agar colony formation assay

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [13]

• Molecule Alteration: Complex-indel; p.L485_P490delinsY (c.1453_1470delinsTAT)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• 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

Key Molecule: GTPase Nras (NRAS) [16]

• Molecule Alteration: Missense mutation; p.Q61K (c.181C>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: SW1271 cells; Lung; Homo sapiens (Human); CVCL_1716
• In Vitro Model: H2347 cells; Lung; Homo sapiens (Human); CVCL_1550
• In Vitro Model: H2087 cells; Lymph node; Homo sapiens (Human); CVCL_1524
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Cell Titer blue reagent assay
• Mechanism Description: The missense mutation p.Q61K (c.181C>A) in gene NRAS cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: Serine/threonine-protein kinase STK11 (STK11) [17]

• Molecule Alteration: Nonsense; p.Q37* (c.109C>T)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MEK signaling pathway; Inhibition; hsa04011
• In Vitro Model: H292 cells; Lung; Homo sapiens (Human); CVCL_0455
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: H157 cells; Lung; Homo sapiens (Human); CVCL_2458
• In Vitro Model: H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Calu-3 cells; Lung; Homo sapiens (Human); CVCL_0609
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: HCC515 cells; Lymph node; Homo sapiens (Human); CVCL_5136
• In Vitro Model: HCC2935 cells; Lung; Homo sapiens (Human); CVCL_1265
• In Vitro Model: HCC193 cells; Lung; Homo sapiens (Human); CVCL_5130
• In Vitro Model: HCC15 cells; Lung; Homo sapiens (Human); CVCL_2057
• In Vitro Model: H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vitro Model: H2122 cells; Pleural effusion; Homo sapiens (Human); CVCL_1531
• In Vitro Model: H2085 cells; Lung; Homo sapiens (Human); CVCL_1523
• In Vitro Model: H1993 cells; Lymph node; Homo sapiens (Human); CVCL_1512
• In Vitro Model: H1435 cells; Lung; Homo sapiens (Human); CVCL_1470
• In Vitro Model: H1395 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: Calu-6 cells; Lung; Homo sapiens (Human); CVCL_0236
• In Vitro Model: Calu-1 cells; Lung; Homo sapiens (Human); CVCL_0608
• In Vivo Model: NOD-SCID mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Alamar blue proliferation assay

Key Molecule: Serine/threonine-protein kinase STK11 (STK11) [17]

• Molecule Alteration: Nonsense; p.E199* (c.595G>T)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MEK signaling pathway; Inhibition; hsa04011
• In Vitro Model: H292 cells; Lung; Homo sapiens (Human); CVCL_0455
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: H157 cells; Lung; Homo sapiens (Human); CVCL_2458
• In Vitro Model: H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Calu-3 cells; Lung; Homo sapiens (Human); CVCL_0609
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: HCC515 cells; Lymph node; Homo sapiens (Human); CVCL_5136
• In Vitro Model: HCC2935 cells; Lung; Homo sapiens (Human); CVCL_1265
• In Vitro Model: HCC193 cells; Lung; Homo sapiens (Human); CVCL_5130
• In Vitro Model: HCC15 cells; Lung; Homo sapiens (Human); CVCL_2057
• In Vitro Model: H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vitro Model: H2122 cells; Pleural effusion; Homo sapiens (Human); CVCL_1531
• In Vitro Model: H2085 cells; Lung; Homo sapiens (Human); CVCL_1523
• In Vitro Model: H1993 cells; Lymph node; Homo sapiens (Human); CVCL_1512
• In Vitro Model: H1435 cells; Lung; Homo sapiens (Human); CVCL_1470
• In Vitro Model: H1395 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: Calu-6 cells; Lung; Homo sapiens (Human); CVCL_0236
• In Vitro Model: Calu-1 cells; Lung; Homo sapiens (Human); CVCL_0608
• In Vivo Model: NOD-SCID mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Alamar blue proliferation assay

Key Molecule: Serine/threonine-protein kinase STK11 (STK11) [17]

• Molecule Alteration: Nonsense; p.W332* (c.995G>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MEK signaling pathway; Inhibition; hsa04011
• In Vitro Model: H292 cells; Lung; Homo sapiens (Human); CVCL_0455
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: H157 cells; Lung; Homo sapiens (Human); CVCL_2458
• In Vitro Model: H23 cells; Lung; Homo sapiens (Human); CVCL_1547
• In Vitro Model: Calu-3 cells; Lung; Homo sapiens (Human); CVCL_0609
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: HCC515 cells; Lymph node; Homo sapiens (Human); CVCL_5136
• In Vitro Model: HCC2935 cells; Lung; Homo sapiens (Human); CVCL_1265
• In Vitro Model: HCC193 cells; Lung; Homo sapiens (Human); CVCL_5130
• In Vitro Model: HCC15 cells; Lung; Homo sapiens (Human); CVCL_2057
• In Vitro Model: H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vitro Model: H2122 cells; Pleural effusion; Homo sapiens (Human); CVCL_1531
• In Vitro Model: H2085 cells; Lung; Homo sapiens (Human); CVCL_1523
• In Vitro Model: H1993 cells; Lymph node; Homo sapiens (Human); CVCL_1512
• In Vitro Model: H1435 cells; Lung; Homo sapiens (Human); CVCL_1470
• In Vitro Model: H1395 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: Calu-6 cells; Lung; Homo sapiens (Human); CVCL_0236
• In Vitro Model: Calu-1 cells; Lung; Homo sapiens (Human); CVCL_0608
• In Vivo Model: NOD-SCID mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Alamar blue proliferation assay

Melanoma [ICD-11: 2C30]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Molecule Alteration: Missense mutation; p.V60E (c.179T>A)
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: WM2664 cells; Skin; Homo sapiens (Human); CVCL_2765
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo 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) [12]

• Molecule Alteration: Missense mutation; p.D594G (c.1781A>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK signaling pathway; Activation; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: H1650 cells; Pleural effusion; Homo sapiens (Human); CVCL_4V01
• In Vitro Model: HTB-56 cells; Pleural effusion; Homo sapiens (Human); CVCL_0236
• In Vitro Model: HTB-38 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HTB-183 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H661 cells; Lymph node; Homo sapiens (Human); CVCL_1577
• In Vitro Model: H508 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: H2405 cells; Lung; Homo sapiens (Human); CVCL_1551
• In Vitro Model: H1666 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: H1395 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: CRL-5944 cells; Ascites; Homo sapiens (Human); CVCL_1551
• In Vitro Model: CRL-5885 cells; Pleural effusion; Homo sapiens (Human); CVCL_1485
• In Vitro Model: CRL-5883 cells; Pleural effusion; Homo sapiens (Human); CVCL_1483
• In Vitro Model: CRL-5868 cells; Lung; Homo sapiens (Human); CVCL_1467
• In Vitro Model: CRL-5803 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: CCL-253 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: CCL-185 cells; Bowel; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Calu-6 cells; Lung; Homo sapiens (Human); CVCL_0236
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: Researchers defined three distinct functional classes of BRAF mutants in human tumours. The mutants activate ERK signalling by different mechanisms that dictate their sensitivity to therapeutic inhibitors of the pathway.

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [18]

• Molecule Alteration: Missense mutation; p.L597Q (c.1790T>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [8]

• Molecule Alteration: Missense mutation; p.K601E (c.1801A>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Melanoma thyroid metastasis; N.A.
• 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: Serine/threonine-protein kinase B-raf (BRAF) [19]

• Molecule Alteration: Missense mutation; p.K601E (c.1801A>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [19]

• Molecule Alteration: Missense mutation; p.L597R (c.1790T>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Whole-gene resequencing assay

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [19]

• Molecule Alteration: Missense mutation; p.V600R (c.1798_1799delGTinsAG)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [20]

• Molecule Alteration: Missense mutation; p.L597V (c.1789C>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Skin; N.A.
• Experiment for Molecule Alteration: Tumour genotyping assay
• Mechanism Description: The missense mutation p.L597V (c.1789C>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) [8]

• Molecule Alteration: Missense mutation; p.L597S (c.1789_1790delCTinsTC)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Melanoma thyroid metastasis; N.A.
• 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) [21]

• Molecule Alteration: Missense mutation; p.L597S (c.1789_1790delCTinsTC)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: Skin sample; N.A.
• In Vivo Model: Mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Crystal violet staining assay

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [22]

• Molecule Alteration: Missense mutation; p.D594V (c.1781A>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.D594V (c.1781A>T) in gene BRAF cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [23]

• Molecule Alteration: Synonymous; p.K601K (c.1803A>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [21]

• Molecule Alteration: Synonymous; p.L597L (c.1791A>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [19]

• Molecule Alteration: Missense mutation; p.K601R (c.1802A>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [20]

• Molecule Alteration: Missense mutation; p.L597R (c.1790T>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293H cells; Fetal kidney; Homo sapiens (Human); CVCL_ZK99
• Experiment for Molecule Alteration: Whole genome sequencing assay

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [24]

• Molecule Alteration: Missense mutation; p.V600K (c.1798_1799delGTinsAA)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: PI3-kinase alpha (PIK3CA) [10]

• Molecule Alteration: Missense mutation; p.N345K (c.1035T>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• 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) [10]

• Molecule Alteration: Missense mutation; p.E542K (c.1624G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• 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.E542K (c.1624G>A) in gene PIK3CA cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [10]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• 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) [10]

• Molecule Alteration: Missense mutation; p.Q546K (c.1636C>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• 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) [10]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• 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) [10]

• Molecule Alteration: Missense mutation; p.H1047L (c.3140A>T)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• 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.H1047L (c.3140A>T) in gene PIK3CA cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Key Molecule: PI3-kinase alpha (PIK3CA) [10]

• Molecule Alteration: Missense mutation; p.G1049R (c.3145G>C)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• 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

Ovarian cancer [ICD-11: 2C73]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [13]

• Molecule Alteration: IF-deletion; p.N486_P490delNVTAP (c.1457_1471del15)
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• 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

Bladder cancer [ICD-11: 2C94]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [25]

• Molecule Alteration: Other; .
• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data

Uveal melanoma [ICD-11: 2D0Y]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) [26]

• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell Titer-blue assay
• Mechanism Description: The missense mutation p.Q209L (c.626A>T) in gene GNA11 cause the sensitivity of Trametinib by unusual activation of pro-survival pathway

Head and neck cancer [ICD-11: 2D42]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Transcriptional coactivator YAP1 (YAP1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• In Vitro Model: SH-1-V5 cells; Esophagus; Homo sapiens (Human); N.A.
• In Vivo Model: Patient-derived xenografts in female NSG mouse model; Mus musculus
• Mechanism Description: Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas. This study identify a Yap1-dependent resistance to trametinib therapy in HNSCCs. Combined Yap1 and MEK targeting may represent a strategy to enhance HNSCC response.

Lymphatic system cancer [ICD-11: 2E81]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [27]

• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Skin; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

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