Cutaneous Manifestations of Vemurafenib Therapy for Metastatic Melanoma

May 2015 | Volume 14 | Issue 5 | Case Reports | 509 | Copyright © May 2015

Joshua L. Owen BS, Isha E. Lopez MD, and Seemal R. Desai MD

Department of Dermatology, University of Texas Southwestern Medical School, Dallas, TX

Vemurafenib, a BRAF inhibitor, is FDA-approved for the treatment of metastatic melanoma in patients who harbor the BRAF V600E mutation. By inhibiting BRAF, vemurafenib prevents the mitogen-activated protein kinase (MAPK) pathway from driving melanoma growth. Here we present a patient with paradoxical activation of the MAPK pathway by vemurafenib, ultimately resulting in deleterious cutaneous manifestations. An emphasis on close follow-up is warranted for new or changing lesions for patients on this medication and other BRAF inhibitors.

J Drugs Dermatol. 2015;14(5):509-510.


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.