A Proposed Mechanism Behind SCC Formation in Vemurafenib Recipients

The high response rate to the recently FDA-approved BRAF inhibitor vemurafenib is an eagerly anticipated development in melanoma therapy. BRAF functions in the signaling cascade between RAS (upstream) and ERK (downstream), ultimately resulting in proliferation. Cancer cells that bear BRAF mutations have high ERK activity. Although adverse cutaneous drug reactions are common, vemurafenib has the interesting effect of inducing cutaneous squamous cell carcinomas (cSCCs) and keratoacanthomas (KAs) that do not bear BRAF mutations. These lesions typically arise within weeks of initiation of therapy, often in sun-exposed areas. The prevailing hypothesis is that in the context of a hyperactive mutant RAS gene and a normal BRAF gene, BRAF inhibitors…