Anti-VEGF therapy revived by c-Met inhibition, but is c-Met the answer?

Cancer Discov. 2012 Mar;2(3):211-3. doi: 10.1158/2159-8290.CD-12-0037.

Abstract

A new study by Sennino and colleagues demonstrates that selective VEGF inhibition via the use of an anti-VEGF antibody is sufficient to increase invasion and metastasis in a c-Met-dependent manner. Anti-VEGF therapy induced tumor hypoxia, hypoxia-inducible factor 1α, and c-Met activation in the RIP-Tag2 model of neuroendocrine pancreatic cancer. Selective c-Met inhibition was sufficient to block these effects, providing a potential mechanism for and solution to overcome increased invasion in the face of anti-VEGF therapy.

Publication types

  • Comment

MeSH terms

  • Anilides / pharmacology*
  • Animals
  • Antibodies, Neutralizing / pharmacology*
  • Humans
  • Neuroendocrine Tumors / drug therapy*
  • Pancreatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Pyridines / pharmacology*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Anilides
  • Antibodies, Neutralizing
  • Pyridines
  • Vascular Endothelial Growth Factor A
  • cabozantinib
  • Proto-Oncogene Proteins c-met