Microenvironment-mediated resistance to anticancer therapies

Cell Res. 2013 Feb;23(2):179-81. doi: 10.1038/cr.2012.123. Epub 2012 Sep 4.

Abstract

Resistance to molecularly targeted therapies can result from genomic alterations in the tumor cells that reactivate oncogenic signaling. Less is known of tumor cell-extrinsic mechanisms of resistance to targeted therapies. Two recent studies have identified HGF as a soluble factor capable of mediating resistance to BRAF and HER2 inhibitors in a paracrine manner. These new findings suggest an important role for the tumor microenvironment in mediating resistance to molecularly targeted therapies.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Resistance, Neoplasm
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction / drug effects
  • Tumor Microenvironment*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Hepatocyte Growth Factor
  • Receptor, ErbB-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf