Development of c-MET pathway inhibitors

Expert Opin Investig Drugs. 2011 Sep;20(9):1225-41. doi: 10.1517/13543784.2011.600687. Epub 2011 Jul 11.

Abstract

Introduction: The aberrantly upregulated c-mesenchymal-epithelia transition factor (c-MET) signaling pathway has been considered to be an attractive target for cancer intervention owing to the important roles it plays in tumor formation, progression, metastasis, angiogenesis and drug resistance. Based on the historical preclinical evidence, a number of c-MET pathway targeted agents are being developed in the clinic, and recent clinical data have begun to provide some insight into which tumor types and patient populations a c-MET pathway inhibitor may be beneficial for.

Areas covered: Through reviewing recent publications in the literature and information disclosed in other public forums, we describe the current understanding of c-MET biology in human malignancies and discuss the latest progress in the development of c-MET pathway inhibitors for cancer treatment.

Expert opinion: The c-MET pathway inhibitors currently being evaluated in the clinic have demonstrated compelling evidence of clinical activity in different cancer types and may provide significant therapeutic opportunities. The challenges, however, are to identify the tumor types and patient populations that benefit most, and find the most effective combinations of therapies while minimizing potential toxicity.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy
  • Hepatocyte Growth Factor / physiology
  • Humans
  • Kidney Neoplasms / drug therapy
  • Lung Neoplasms / drug therapy
  • Neoplasm Metastasis / drug therapy
  • Neoplasms / drug therapy
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / physiology
  • Signal Transduction / drug effects*
  • Thyroid Neoplasms / drug therapy

Substances

  • Angiogenesis Inhibitors
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met