Targeting the c-MET signaling pathway for cancer therapy

Expert Opin Investig Drugs. 2008 Jul;17(7):997-1011. doi: 10.1517/13543784.17.7.997.


Background: In many human cancers, c-MET is activated via receptor overexpression, amplification, mutation and/or a ligand-dependent autocrine/paracrine loop. These biochemical and genetic abnormalities have been correlated with poor clinical outcomes and drug resistance in cancer patients. Preclinical studies suggest that targeting aberrant c-MET signaling could be an attractive therapy in cancer, but this notion has only recently been tested in the clinic.

Objectives: To describe the biological aspects of the c-MET signaling pathway and to discuss recent progress and possible future trends in the development of agents that target the c-MET pathway, with an emphasis on small-molecule c-MET kinase inhibitors.

Method: A review of relevant publications, including published articles in literature, reports at scientific meetings, and information available through the Internet.

Results/conclusion: The dysregulated c-MET pathway represents a promising target for cancer drug development. The agents that target the c-MET pathway have demonstrated impressive evidence of early clinical activity and may have a significant therapeutic potential.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Hepatocyte Growth Factor / chemistry
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-met / chemistry
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction / drug effects*


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