Drug Information

Drug (ID: DG01505) and It's Reported Resistant Information

• Name: Selumetinib
• Synonyms: Selumetinib; 606143-52-6; AZD6244; AZD 6244; ARRY-142886; 5-[(4-BROMO-2-CHLOROPHENYL)AMINO]-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZIMIDAZOLE-6-CARBOXAMIDE; AZD-6244; Selumetinib (AZD6244); ARRY 142886; AZD6244 (Selumetinib); ARRY-886; UNII-6UH91I579U; 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide; 5-(4-broMo-2-chlorophenylaMino)-4-fluoro-N-(2-hydroxyethoxy)-1-Methyl-1H-benzo[d]iMidazole-6-carboxaMide; CHEMBL1614701; CHEBI:90227; 6UH91I579U; NCGC00189073-01; NCGC00189073-02; C17H15BrClFN4O3; 6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide; DSSTox_CID_28870; DSSTox_RID_83139; DSSTox_GSID_48944; 1H-Benzimidazole-6-carboxamide, 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-; 6-[(4-bromo-2-chlorophenyl)amino]-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide; AZD 6244;5-((4-Bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide;6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide; CAS-606143-52-6; ARRY142886; Selumetinib [USAN:INN]; selumetinibum; Koselugo; 1H-Benzimidazole-6-carboxamide, 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-; 3EW; Selumetinib (USAN/INN); AZD6244 - Selumetinib; AZD 6244 (Selumetinib); SCHEMBL155456; GTPL5665; QCR-91; Selumetinib, ARRY-142886; DTXSID3048944; EX-A020; SYN1016; BCPP000367; HMS3244G03; HMS3244G04; HMS3244H03; HMS3265K01; HMS3265K02; HMS3265L01; HMS3265L02; HMS3654O03; NSC 741O78; AOB87732; BCP01739; Tox21_113362; BDBM50355497; MFCD11977472; NSC741078; NSC800882; s1008; ZINC31773258; AKOS015904255; Tox21_113362_1; BCP9000354; CCG-264774; CS-0059; DB11689; EX-8621; NSC-741078; NSC-800882; SB14707; NCGC00189073-07; AC-25059; AM808016; AZD6244,Selumetinib, ARRY-142886; BC004624; HY-50706; Selumetinib (ARRY142886/AZD6244); AZD6244 (Selumetinib,ARRY-142886); FT-0674552; SW202561-3; X2640; D09666; 143A526; Q-101405; Q7448840; BRD-K57080016-001-01-9; 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide; 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy -ethoxy)-amide; 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid(2-hydroxy-ethoxy)-amide; 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide; 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid(2-hydroxyethoxy)-amide; 6-(4-bromo-2chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide
• Indication:
  In total 2 Indication(s)
  Parkinson disease [ICD-11: 8A00]; Phase 3; [1]
  Parkinson disease [ICD-11: 8A00]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Acute myeloid leukemia [ICD-11: 2A60]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (5 diseases)
  Bladder cancer [ICD-11: 2C94]; [3]
  Endometrial cancer [ICD-11: 2C76]; [4]
  Lung cancer [ICD-11: 2C25]; [5]
  Melanoma [ICD-11: 2C30]; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [6]
• Target: 5-HT 2A receptor (HTR2A); 5HT2A_HUMAN; [7]
• Formula: 6
• IsoSMILES: CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO
• InChI: InChI=1S/C17H15BrClFN4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
• InChIKey: CYOHGALHFOKKQC-UHFFFAOYSA-N
• PubChem CID: 10127622
• ChEBI ID: CHEBI:90227
• TTD Drug ID: D0J8JP
• DrugBank ID: DB11689

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

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [7]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [7]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
• Experimental Note: Identified from the Human Clinical Data

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [6]

• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [6]

• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [6]

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

• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [6]

• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [6]

• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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) [6]

• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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

Acute myeloid leukemia [ICD-11: 2A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [2]

• Molecule Alteration: IF-deletion; p.Q569_G613 (c.1705_1837)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood; N.A.
• Experiment for Molecule Alteration: Gentra puregene assay
• Experiment for Drug Resistance: p-ERK1/2 and p-mTOR analysis

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) [2]

• Molecule Alteration: Synonymous; p.L862L (c.2586G>C)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood; N.A.
• Experiment for Molecule Alteration: Gentra puregene assay
• Experiment for Drug Resistance: p-ERK1/2 and p-mTOR analysis

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) [8]

• 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: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NUGC-4 cells; Lymph node; Homo sapiens (Human); CVCL_3082/CVCL_8372
• Experiment for Molecule Alteration: Multiplex deep sequencing of MAP2K1 cDNAs assay
• Experiment for Drug Resistance: Focus formation assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of Selumetinib by aberration of the drug's therapeutic target

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Molecule Alteration: Missense mutation; p.T790M (c.2369C>T)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vivo Model: BALB/C nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Immunohistochemistry assay
• Experiment for Drug Resistance: MTT assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [9]

• 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: MAPK/ERK kinase 1 (MEK1) [10]

• Molecule Alteration: Missense mutation; p.K57N (c.171G>T)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue staining assay
• Mechanism Description: The missense mutation p.K57N (c.171G>T) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [10]

• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue staining 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: GTPase Nras (NRAS) [11]

• 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 Selumetinib by unusual activation of pro-survival pathway

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) [12]

• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Resistant 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
• 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.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [12]

• Molecule Alteration: Missense mutation; p.I103N (c.308T>A)
• Resistant 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
• 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 Selumetinib by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [12]

• Molecule Alteration: Missense mutation; p.L115P (c.344T>C)
• Resistant 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
• 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 Selumetinib by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [12]

• Molecule Alteration: Missense mutation; p.P124S (c.370C>T)
• Resistant 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
• 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.P124S (c.370C>T) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target

Key Molecule: MAPK/ERK kinase 1 (MEK1) [12]

• Molecule Alteration: Missense mutation; p.P124L (c.371C>T)
• Resistant 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
• 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.P124L (c.371C>T) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Nras (NRAS) [1]

• Molecule Alteration: Missense mutation; p.Q61L (c.182A>T)
• Resistant 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
• In Vitro Model: Sk-Mel28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: WM2664 cells; Skin; Homo sapiens (Human); CVCL_2765
• In Vitro Model: SkMEL 30 cells; Skin; Homo sapiens (Human); CVCL_0039
• In Vitro Model: SkMEL 2 cells; Skin; Homo sapiens (Human); CVCL_0069
• In Vitro Model: SH4 cells; Skin; Mus musculus (Mouse); CVCL_7702
• In Vitro Model: MEXF-535 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: MEXF-1792 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: MEXF-1341 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: M14 cells; Hypodermis; Homo sapiens (Human); CVCL_1395
• In Vitro Model: GAK cells; Lnguinal lymph node; Homo sapiens (Human); CVCL_1225
• In Vitro Model: Colo829 cells; Skin; Homo sapiens (Human); CVCL_1137
• In Vivo Model: Female NIH nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
• Experiment for Drug Resistance: CellTiter-Glo assay; Enzymatic kinase assay

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) [13]

• Molecule Alteration: Missense mutation; p.Q209P (c.626A>C)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) [13]

• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) [13]

• Molecule Alteration: Missense mutation; p.Q209P (c.626A>C)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) [13]

• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: GTPase Nras (NRAS) [14]

• Molecule Alteration: Missense mutation; p.Q61L (c.182A>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Drug Resistance: MTD assay
• Mechanism Description: The missense mutation p.Q61L (c.182A>T) in gene NRAS cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: GTPase Nras (NRAS) [1]

• Molecule Alteration: Missense mutation; p.Q61K (c.181C>A)
• 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
• In Vitro Model: Sk-Mel28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: WM2664 cells; Skin; Homo sapiens (Human); CVCL_2765
• In Vitro Model: SkMEL 30 cells; Skin; Homo sapiens (Human); CVCL_0039
• In Vitro Model: SkMEL 2 cells; Skin; Homo sapiens (Human); CVCL_0069
• In Vitro Model: SH4 cells; Skin; Mus musculus (Mouse); CVCL_7702
• In Vitro Model: MEXF-535 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: MEXF-1792 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: MEXF-1341 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: M14 cells; Hypodermis; Homo sapiens (Human); CVCL_1395
• In Vitro Model: GAK cells; Lnguinal lymph node; Homo sapiens (Human); CVCL_1225
• In Vitro Model: Colo829 cells; Skin; Homo sapiens (Human); CVCL_1137
• In Vivo Model: Female NIH nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
• Experiment for Drug Resistance: CellTiter-Glo assay; Enzymatic kinase assay

Key Molecule: GTPase Nras (NRAS) [14]

• Molecule Alteration: Missense mutation; p.Q61R (c.182A>G)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Drug Resistance: MTD assay
• Mechanism Description: The missense mutation p.Q61R (c.182A>G) in gene NRAS cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: GTPase Nras (NRAS) [15]

• Molecule Alteration: Missense mutation; p.Q61K (c.181C>A)
• 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: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.Q61K (c.181C>A) in gene NRAS cause the sensitivity of Selumetinib by aberration of the drug's therapeutic target

Key Molecule: GTPase Nras (NRAS) [1]

• Molecule Alteration: Missense mutation; p.G13D (c.38G>A)
• 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
• In Vitro Model: Sk-Mel28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: WM2664 cells; Skin; Homo sapiens (Human); CVCL_2765
• In Vitro Model: SkMEL 30 cells; Skin; Homo sapiens (Human); CVCL_0039
• In Vitro Model: SkMEL 2 cells; Skin; Homo sapiens (Human); CVCL_0069
• In Vitro Model: SH4 cells; Skin; Mus musculus (Mouse); CVCL_7702
• In Vitro Model: MEXF-535 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: MEXF-1792 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: MEXF-1341 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: M14 cells; Hypodermis; Homo sapiens (Human); CVCL_1395
• In Vitro Model: GAK cells; Lnguinal lymph node; Homo sapiens (Human); CVCL_1225
• In Vitro Model: Colo829 cells; Skin; Homo sapiens (Human); CVCL_1137
• In Vivo Model: Female NIH nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
• Experiment for Drug Resistance: CellTiter-Glo assay; Enzymatic kinase assay

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Molecule Alteration: Missense mutation; p.D259Y (c.775G>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
• In Vitro Model: Sk-Mel28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: WM2664 cells; Skin; Homo sapiens (Human); CVCL_2765
• In Vitro Model: SkMEL 30 cells; Skin; Homo sapiens (Human); CVCL_0039
• In Vitro Model: SkMEL 2 cells; Skin; Homo sapiens (Human); CVCL_0069
• In Vitro Model: SH4 cells; Skin; Mus musculus (Mouse); CVCL_7702
• In Vitro Model: MEXF-535 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: MEXF-1792 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: MEXF-1341 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: M14 cells; Hypodermis; Homo sapiens (Human); CVCL_1395
• In Vitro Model: GAK cells; Lnguinal lymph node; Homo sapiens (Human); CVCL_1225
• In Vitro Model: Colo829 cells; Skin; Homo sapiens (Human); CVCL_1137
• In Vivo Model: Female NIH nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
• Experiment for Drug Resistance: CellTiter-Glo assay; Enzymatic kinase assay

Ovarian cancer [ICD-11: 2C73]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [16]

• Molecule Alteration: IF-deletion; p.Q56_V60delQKQKV (c.166_180del15)
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ovary; N.A.
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome analysis
• Experiment for Drug Resistance: Colony formation assay

Endometrial cancer [ICD-11: 2C76]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [4]

• Molecule Alteration: Missense mutation; p.S252W (c.755C>G)
• Resistant Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT-4 cells; Urinary bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT-4 cells; Urinary bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: SUM-52PE cells; Pleural effusion; Homo sapiens (Human); CVCL_3425
• In Vitro Model: NCI-H1581 cells; Lung; Homo sapiens (Human); CVCL_1479
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: KMS-11 cells; Pleural effusion; Homo sapiens (Human); CVCL_2989
• In Vitro Model: HSC-39 cells; Ascites; Homo sapiens (Human); CVCL_A385
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vitro Model: AN3 CA cells; Endometrium; Homo sapiens (Human); CVCL_0028
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: KATO-III cells; Pleural effusion; Homo sapiens (Human); CVCL_0371
• In Vitro Model: AN3 CA cells; Endometrium; Homo sapiens (Human); CVCL_0028
• Experiment for Molecule Alteration: Microarray assay; Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Bladder cancer [ICD-11: 2C94]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.S310F (c.929C>T)
• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: SW780 cells; Bladder; Homo sapiens (Human); CVCL_1728
• In Vitro Model: HT1376 cells; Bladder; Homo sapiens (Human); CVCL_1292
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: TCCSuP cells; Bladder; Homo sapiens (Human); CVCL_1738
• In Vitro Model: UM-UC3 cells; Urinary bladder; Homo sapiens (Human); CVCL_1783
• In Vitro Model: WH cells; Bladder; Homo sapiens (Human); CVCL_0C39
• In Vitro Model: VM-CUBIII cells; Urinary bladder; Homo sapiens (Human); CVCL_9830
• In Vitro Model: VM-CUBII cells; Urinary bladder; Homo sapiens (Human); CVCL_9829
• In Vitro Model: VM-CUBI cells; Obturator lymph node; Homo sapiens (Human); CVCL_1786
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: TSU-PR1 cells; Urinary bladder; Homo sapiens (Human); CVCL_4014
• In Vitro Model: SW1710 cells; Bladder; Homo sapiens (Human); CVCL_1721
• In Vitro Model: SD cells; Bladder; Homo sapiens (Human); CVCL_W902
• In Vitro Model: KU-19 cells; Blood; Bos taurus (Bovine); CVCL_VN09
• In Vitro Model: JO'N cells; Urinary bladder; Homo sapiens (Human); CVCL_M891
• In Vitro Model: JMSU-1 cells; Ascites; Homo sapiens (Human); CVCL_2081
• In Vitro Model: HT1197 cells; Urinary bladder; Homo sapiens (Human); CVCL_1291
• In Vitro Model: DSH1 cells; Urinary bladder; Homo sapiens (Human); CVCL_1182
• In Vitro Model: CAL-29 cells; Urinary bladder; Homo sapiens (Human); CVCL_1808
• In Vitro Model: BFTC-905 cells; Urinary bladder; Homo sapiens (Human); CVCL_1083
• In Vitro Model: BC-3C cells; Urinary bladder; Homo sapiens (Human); CVCL_1958
• In Vitro Model: 97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: 97-24 cells; Bladder; Homo sapiens (Human); CVCL_8621
• In Vitro Model: 97-18 cells; Bladder; Homo sapiens (Human); CVCL_8619
• In Vitro Model: 97-1 cells; Bladder; Homo sapiens (Human); CVCL_8616
• In Vitro Model: 96-1 cells; Bladder; Homo sapiens (Human); CVCL_8609
• In Vitro Model: 94-10 cells; Bladder; Homo sapiens (Human); CVCL_8608
• In Vitro Model: 647V cells; Urinary bladder; Homo sapiens (Human); CVCL_1049
• In Vitro Model: 253J cells; Lymph node; Homo sapiens (Human); CVCL_7935/CVCL_7938
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.S653C (c.1958C>G)
• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: SW780 cells; Bladder; Homo sapiens (Human); CVCL_1728
• In Vitro Model: HT1376 cells; Bladder; Homo sapiens (Human); CVCL_1292
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: TCCSuP cells; Bladder; Homo sapiens (Human); CVCL_1738
• In Vitro Model: UM-UC3 cells; Urinary bladder; Homo sapiens (Human); CVCL_1783
• In Vitro Model: WH cells; Bladder; Homo sapiens (Human); CVCL_0C39
• In Vitro Model: VM-CUBIII cells; Urinary bladder; Homo sapiens (Human); CVCL_9830
• In Vitro Model: VM-CUBII cells; Urinary bladder; Homo sapiens (Human); CVCL_9829
• In Vitro Model: VM-CUBI cells; Obturator lymph node; Homo sapiens (Human); CVCL_1786
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: TSU-PR1 cells; Urinary bladder; Homo sapiens (Human); CVCL_4014
• In Vitro Model: SW1710 cells; Bladder; Homo sapiens (Human); CVCL_1721
• In Vitro Model: SD cells; Bladder; Homo sapiens (Human); CVCL_W902
• In Vitro Model: KU-19 cells; Blood; Bos taurus (Bovine); CVCL_VN09
• In Vitro Model: JO'N cells; Urinary bladder; Homo sapiens (Human); CVCL_M891
• In Vitro Model: JMSU-1 cells; Ascites; Homo sapiens (Human); CVCL_2081
• In Vitro Model: HT1197 cells; Urinary bladder; Homo sapiens (Human); CVCL_1291
• In Vitro Model: DSH1 cells; Urinary bladder; Homo sapiens (Human); CVCL_1182
• In Vitro Model: CAL-29 cells; Urinary bladder; Homo sapiens (Human); CVCL_1808
• In Vitro Model: BFTC-905 cells; Urinary bladder; Homo sapiens (Human); CVCL_1083
• In Vitro Model: BC-3C cells; Urinary bladder; Homo sapiens (Human); CVCL_1958
• In Vitro Model: 97-7 cells; Bladder; Homo sapiens (Human); CVCL_8625
• In Vitro Model: 97-24 cells; Bladder; Homo sapiens (Human); CVCL_8621
• In Vitro Model: 97-18 cells; Bladder; Homo sapiens (Human); CVCL_8619
• In Vitro Model: 97-1 cells; Bladder; Homo sapiens (Human); CVCL_8616
• In Vitro Model: 96-1 cells; Bladder; Homo sapiens (Human); CVCL_8609
• In Vitro Model: 94-10 cells; Bladder; Homo sapiens (Human); CVCL_8608
• In Vitro Model: 647V cells; Urinary bladder; Homo sapiens (Human); CVCL_1049
• In Vitro Model: 253J cells; Lymph node; Homo sapiens (Human); CVCL_7935/CVCL_7938
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay

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 alpha-q (GNAQ) [17]

• 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
• In Vitro Model: Omm13 cells; N.A.; .; N.A.
• In Vitro Model: Mel270 cells; Skin; Homo sapiens (Human); CVCL_C302
• In Vitro Model: Mel202 cells; Eye; Homo sapiens (Human); CVCL_C301
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.Q209L (c.626A>T) in gene GNAQ cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Key Molecule: Guanine nucleotide-binding protein alpha-q (GNAQ) [17]

• Molecule Alteration: Missense mutation; p.Q209P (c.626A>C)
• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Omm13 cells; N.A.; .; N.A.
• In Vitro Model: Mel270 cells; Skin; Homo sapiens (Human); CVCL_C302
• In Vitro Model: Mel202 cells; Eye; Homo sapiens (Human); CVCL_C301
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.Q209P (c.626A>C) in gene GNAQ cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Thyroid cancer [ICD-11: 2D10]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: BRAF/MEK/MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: BCPAP cells; Thyroid; Homo sapiens (Human); CVCL_0153
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• In Vitro Model: C643 cells; Thyroid gland; Homo sapiens (Human); CVCL_5969
• In Vitro Model: CAL62 cells; Thyroid gland; Homo sapiens (Human); CVCL_1112
• In Vivo Model: Athymic nude mouse PDX xenografts model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay; Immunoprecipitation assy
• Experiment for Drug Resistance: SRB staining assay; Promega assay
• Mechanism Description: Activation of the Mitogen Activated Protein (MAP) Kinase pathway was increased in all four of the dasatinib-resistant cell lines, likely due to B-Raf and c-Raf dimerization. Furthermore, MAP2K1/MAP2K2 (MEK1/2) inhibition restored sensitivity in all four of the dasatinib-resistant cell lines, and overcome acquired resistance to dasatinib in the RAS-mutant Cal62 cell line, in vivo. Together, these studies demonstrate that acquisition of the c-Src gatekeeper mutation and MAP Kinase pathway signaling play important roles in promoting resistance to the Src inhibitor, dasatinib.

References

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