Drug development of MET inhibitors: targeting oncogene addiction and expedience

Nat Rev Drug Discov. 2008 Jun;7(6):504-16. doi: 10.1038/nrd2530.


The MET tyrosine kinase stimulates cell scattering, invasion, protection from apoptosis and angiogenesis, thereby acting as a powerful expedient for cancer dissemination. MET can also be genetically selected for the long-term maintenance of the primary transformed phenotype, and some tumours appear to be dependent on (or 'addicted' to) sustained MET activity for their growth and survival. Because of its dual role as an adjuvant, pro-metastatic gene for some tumour types and as a necessary oncogene for others, MET is a versatile candidate for targeted therapeutic intervention. Here we discuss recent progress in the development of molecules that inhibit MET function and consider their application in a subset of human tumours that are potentially responsive to MET-targeted therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Drug Design*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Hepatocyte Growth Factor / antagonists & inhibitors
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Molecular Structure
  • Neoplasms* / drug therapy
  • Neoplasms* / enzymology
  • Neoplasms* / genetics
  • Oncogenes*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / genetics


  • Antineoplastic Agents
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met