Showering c-MET-dependent cancers with drugs

Curr Opin Genet Dev. 2008 Feb;18(1):87-96. doi: 10.1016/j.gde.2008.02.001. Epub 2008 Apr 9.


The receptor tyrosine kinase, c-MET and its ligand hepatocyte growth factor/scatter factor (HGF/SF) have become leading candidates for targeted cancer therapies. Inappropriate c-MET signaling through autocrine, paracrine, amplification, and mutational activation occurs in virtually all types of solid tumors (, contributing to one or a combination of proliferative, invasive, survival, or angiogenic cancer phenotypes. c-MET and HGF/SF participate in all stages of malignant progression and represent promising drug targets in a variety of cancer types, including carcinomas, sarcomas, and brain tumors. While many are in pre-clinical testing, a few inhibitors have entered clinical trials. With hundreds of thousands of potential responding cancers that express c-MET, the interest in this molecule as a drug target is not surprising. However, the cognate c-MET diagnostic tests lag behind. In addition, despite the great enthusiasm based on response rates in phase I trials, there is a need for caution. It is almost without question that combination therapies with c-MET-HGF/SF inhibitors will be required for most cancers to achieve a cytotoxic tumor response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Hepatocyte Growth Factor / antagonists & inhibitors
  • Humans
  • Neoplasm Metastasis
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / physiology
  • Signal Transduction / drug effects


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