Modulation of c-Met signaling and cellular sensitivity to radiation: potential implications for therapy

Cancer. 2013 May 15;119(10):1768-75. doi: 10.1002/cncr.27965. Epub 2013 Feb 19.

Abstract

The c-Met/hepatocyte growth factor receptor and its family members are known to promote cancer cell migration and invasion. Signaling within and beyond this pathway contributes to the systemic spread of metastases through induction of the epithelial-mesenchymal transition, a process also implicated in mediating resistance to current anticancer therapies, including radiation. Induction of c-Met has also been observed after irradiation, suggesting that c-Met participates in radiation-induced disease progression through the epithelial-mesenchymal transition. Therefore, c-Met inhibition is an attractive target for potentially mitigating radiation resistance. This article summarizes key findings regarding crosstalk between radiotherapy and c-Met and discusses studies performed to date in which c-Met inhibition was used as a strategy to increase cellular radiosensitivity.

Publication types

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

MeSH terms

  • Anilides / pharmacology
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Cell Movement / radiation effects
  • DNA Damage / radiation effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / radiation effects
  • Erlotinib Hydrochloride
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness
  • Neoplasms / metabolism*
  • Neovascularization, Pathologic
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / metabolism*
  • Pyridines / pharmacology
  • Pyrrolidinones / pharmacology
  • Quinazolines / pharmacology
  • Quinolines / pharmacology
  • Radiation Tolerance
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects*
  • Up-Regulation

Substances

  • ARQ 197
  • Anilides
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Pyridines
  • Pyrrolidinones
  • Quinazolines
  • Quinolines
  • cabozantinib
  • rilotumumab
  • Erlotinib Hydrochloride
  • MET protein, human
  • Proto-Oncogene Proteins c-met