Drug Information

Drug (ID: DG01892) and It's Reported Resistant Information

• Name: MET inhibitors
• Synonyms: MET inhibitors
• Indication:
  In total 5 Indication(s)
  Squamous head and neck cell carcinom [ICD-11: 2D60]; Approved; [1]
  Breast cancer [ICD-11: 2C60]; Phase 1; [1]
  Renal cell carcinoma [ICD-11: 2C90]; Phase 1; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
  Gastric adenocarcinoma [ICD-11: 2B72]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Lung cancer [ICD-11: 2C25]; [2]
• Target: Vascular endothelial growth factor receptor 2 (KDR); VGFR2_HUMAN; [1]

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

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: Hepatocyte growth factor receptor (MET) [1]

• Molecule Alteration: Missense mutation; p.H1112L (c.3335A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.

Gastric cancer [ICD-11: 2B72]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [3]

• Molecule Alteration: Copy number gain; .
• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Experimental Note: Identified from the Human Clinical Data

Liver cancer [ICD-11: 2C12]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [4]

• Molecule Alteration: Copy number gain; .
• Sensitive Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Experimental Note: Identified from the Human Clinical Data

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Hepatocyte growth factor receptor (MET) [2]

• Molecule Alteration: Missense mutation; p.D1228V (c.3683A>T)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: There is a patient with metastatic NSCLC with MET-mediated resistance to EGFR TKI who responded to treatment with a type I MET inhibitor, savolitinib, given in combination with a third-generation EGFR inhibitor, osimertinib. The patient then developed acquired resistance mediated by a novel MET kinase domain mutation.

Kidney cancer [ICD-11: 2C90]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [5]

• Molecule Alteration: Copy number gain; .
• Sensitive Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Hepatocyte growth factor receptor (MET) [5]

• Molecule Alteration: Missense mutation; p.H1094R (c.3281A>G)
• Sensitive Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Renal cell carcinoma tissue; N.A.
• Mechanism Description: The missense mutation p.H1094R (c.3281A>G) in gene MET cause the sensitivity of MET inhibitors by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [6]

• Molecule Alteration: Missense mutation; p.M1268T (c.3803T>C)
• Sensitive Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human renal cell carcinoma tissue; N.A.
• Mechanism Description: The missense mutation p.M1268T (c.3803T>C) in gene MET cause the sensitivity of MET inhibitors by aberration of the drug's therapeutic target

References

• Ref 1: Abstract 1786: Characterization of the inhibitory capacity of EMD1214063, a novel small molecule inhibitor of the MET hepatocyte growth factor receptor on a panel of MET mutated variants.
• Ref 2: Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer. Cancer Discov. 2016 Dec;6(12):1334-1341. doi: 10.1158/2159-8290.CD-16-0686. Epub 2016 Sep 30.
• Ref 3: Indian J Med Paediatr Oncol. 2015 Apr-Jun;36(2):133-6. doi: 10.4103/0971-5851.158852.
• Ref 4: STATISTICS/DATA TYPE - iGMDR.
• Ref 5: Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinomaJ Clin Oncol. 2013 Jan 10;31(2):181-6. doi: 10.1200/JCO.2012.43.3383. Epub 2012 Dec 3.
• Ref 6: Initial clinical sensitivity and acquired resistance to MET inhibition in MET-mutated papillary renal cell carcinomaJ Clin Oncol. 2013 Jun 1;31(16):e254-8. doi: 10.1200/JCO.2012.46.4289. Epub 2013 Apr 22.