Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug-resistant melanomas.


Journal Article

BRAF mutations in aggressive melanomas result in kinase activation. BRAF inhibitors reduce BRAF(V600E) tumors, but rapid resistance follows. In this issue of the JCI, Ma and colleagues report that vemurafenib activates ER stress and autophagy in BRAF(V600E) melanoma cells, through sequestration of the ER chaperone GRP78 by the mutant BRAF and subsequent PERK activation. In preclinical studies, treating vemurafenib-resistant melanoma with a combination of vemurafenib and an autophagy inhibitor reduced tumor load. Further work is needed to establish clinical relevance of this resistance mechanism and demonstrate efficacy of autophagy and kinase inhibitor combinations in melanoma treatment.

Full Text

Duke Authors

Cited Authors

  • Shenolikar, S

Published Date

  • March 2014

Published In

Volume / Issue

  • 124 / 3

Start / End Page

  • 973 - 976

PubMed ID

  • 24569370

Pubmed Central ID

  • 24569370

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/JCI74609


  • eng

Conference Location

  • United States