Will Hsp90 inhibitors prove effective in BRAF-mutant melanomas?

Clin Cancer Res. 2012 May 1;18(9):2420-2. doi: 10.1158/1078-0432.CCR-12-0626. Epub 2012 Mar 22.

Abstract

The RAF inhibitor vemurafenib has unprecedented activity in BRAF-mutant melanomas, but resistance invariably develops. As Hsp90 is required for the stability of several of the oncoproteins that mediate RAF inhibitor resistance, inhibitors of this cellular chaperone may be effective in patients with intrinsic or acquired resistance to RAF inhibitors.

Publication types

  • Comment

MeSH terms

  • Animals
  • Azabicyclo Compounds / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • Melanoma / drug therapy*
  • Phthalic Acids / pharmacology*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Signal Transduction / drug effects*

Substances

  • Azabicyclo Compounds
  • HSP90 Heat-Shock Proteins
  • Phthalic Acids
  • XL 888
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf