BRAF Inhibitors in Melanoma Management: When Friends Become Foes

J Invest Dermatol. 2022 May;142(5):1256-1259. doi: 10.1016/j.jid.2021.11.005. Epub 2021 Dec 3.

Abstract

The BRAF inhibitor (BRAFi) vemurafenib improves survival of patients with melanoma with BRAFV600E mutations. However, effects of sustained BRAFis on BRAFi-resistant melanomas with dual mutations in BRAF and NRAS are not well characterized. Jandova and Wondrak (2021) report that vemurafenib selectively enhances expression of genes involved in the epithelial-to-mesenchymal transition in BRAFV600E/NRASQ61K melanoma cells, paradoxically promoting tumor growth and metastasis in mice. This preclinical study provides compelling reasons to be cautious in the use of BRAFis in patients with NRAS-driven melanoma.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics
  • Friends
  • Humans
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / metabolism
  • Mice
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf* / genetics
  • Proto-Oncogene Proteins B-raf* / metabolism
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use
  • Vemurafenib / pharmacology
  • Vemurafenib / therapeutic use

Substances

  • Indoles
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf