The HGF-cMET signaling pathway in conferring stromal-induced BRAF-inhibitor resistance in melanoma

Melanoma Res. 2015 Dec;25(6):470-8. doi: 10.1097/CMR.0000000000000194.

Abstract

Genetic heterogeneity in melanoma is well established. Given this, as well as the complexity of mechanisms involved in cancer in vivo, a more complete understanding of the development of resistance requires a closer look at the tumor ecosystem, including the microenvironment. Echoing this more comprehensive approach, a number of recent studies on BRAF-inhibitor resistance have brought our attention back to the tumor microenvironment, particularly through a focus on HGF-cMET signaling - a known means of stromal-parenchymal communication. Our review focuses on the results of these recent investigations, and through a review of relevant HGF-cMET past literature looks to provide a context by which to better understand the role of stromal-parenchymal signaling in BRAF resistance/melanoma progression.

Publication types

  • Review

MeSH terms

  • Drug Resistance, Neoplasm / physiology*
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction / physiology
  • Tumor Microenvironment / physiology*

Substances

  • HGF protein, human
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf