Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032.
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.
Rubinstein
Jill C
JC
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA.
Sznol
Mario
M
Pavlick
Anna C
AC
Ariyan
Stephan
S
Cheng
Elaine
E
Bacchiocchi
Antonella
A
Kluger
Harriet M
HM
Narayan
Deepak
D
Halaban
Ruth
R
D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D013449:Sulfonamides / Q000627:therapeutic use*; D000077484:Vemurafenib
D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf