Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032

J Transl Med. 2010 Jul 14:8:67. doi: 10.1186/1479-5876-8-67.

Abstract

Activating mutations in BRAF kinase are common in melanomas. Clinical trials with PLX4032, the mutant-BRAF inhibitor, show promising preliminary results in patients selected for the presence of V600E mutation. However, activating V600K mutation is the other most common mutation, yet patients with this variant are currently excluded from the PLX4032 trials. Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations.

Publication types

  • Case Reports
  • Editorial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution / genetics
  • Base Sequence
  • DNA Mutational Analysis
  • Humans
  • Indoles / therapeutic use*
  • Melanoma / drug therapy*
  • Melanoma / enzymology
  • Melanoma / genetics*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics*
  • Sulfonamides / therapeutic use*
  • Vemurafenib

Substances

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