Targeting MET in cancer: rationale and progress

Nat Rev Cancer. 2012 Jan 24;12(2):89-103. doi: 10.1038/nrc3205.

Abstract

Uncontrolled cell survival, growth, angiogenesis and metastasis are essential hallmarks of cancer. Genetic and biochemical data have demonstrated that the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the tyrosine kinase MET, have a causal role in all of these processes, thus providing a strong rationale for targeting these molecules in cancer. Parallel progress in understanding the structure and function of HGF/SF, MET and associated signalling components has led to the successful development of blocking antibodies and a large number of small-molecule MET kinase inhibitors. In this Review, we discuss these advances, as well as results from recent clinical studies that demonstrate that inhibiting MET signalling in several types of solid human tumours has major therapeutic value.

Publication types

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

MeSH terms

  • Epithelial-Mesenchymal Transition
  • Hepatocyte Growth Factor / metabolism
  • Hepatocyte Growth Factor / physiology
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Signal Transduction

Substances

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