Mutant BRAF melanomas-dependence and resistance Review uri icon

Overview

MeSH Major

  • Drug Resistance, Neoplasm
  • Melanoma
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf

abstract

  • RAF inhibitors have the unique property of transactivating RAS-dependent RAF dimers in most cells but inhibit RAF/MEK/ERK signaling in cells expressing mutant BRAF, in which RAS activity is too low to support this process. These drugs thus selectively inhibit ERK signaling in tumors with BRAF mutation. RAF inhibitors have remarkable clinical activity in melanomas with BRAFV600E mutations; however, resistance invariably develops. Three recent papers reveal that acquired resistance may be due to mechanisms that cause ERK signaling to become insensitive to RAF inhibitors, or that reduce the dependence of the tumor on ERK signaling through activation of other pathways.

publication date

  • January 18, 2011

Research

keywords

  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2011.01.008

PubMed ID

  • 21251612

Additional Document Info

start page

  • 11

end page

  • 5

volume

  • 19

number

  • 1