Introduction
BRAF is a serine/threonine-protein kinase that regulates the
activation of the MAPK pathway. This pathway is critical
for cellular proliferation and malignant transformation.
BRAF is the most commonly mutated protein kinase in human
cancers, including cutaneous melanomas where 40-60% contain
mutations in BRAF.1-3 Initially described in 2002, vemurafenib is
a selective inhibitor of BRAF that preferentially binds to the most
commonly mutated form of BRAF, valine to glutamate at position
600 (V600E).4 It was approved by FDA in 2011 for the treatment
of metastatic melanoma, which has increased the median overall
survival of individuals with metastatic melanoma from 6-10
months to 16 months.5 Despite inhibiting BRAF and blocking the
downstream activation of the MAPK pathway, patients treated with
vemurafenib have been found to develop both benign and malignant
growths while on treatment.6-9 We present a case illustrating
this paradoxical activation of the MAPK pathway by vemurafenib,
resulting in a multitude of deleterious cutaneous manifestations.
