title: Dermatological adverse events from BRAF inhibitors: a growing problem.
abstract: The development of targeted therapies has ushered in a new era in the management of melanoma. Inhibitors of the RAS-RAF-MEK-ERK pathway have taken the center stage with development at a rapid pace. Vemurafenib was recently approved by regulatory agencies, and other agents (e.g. dabrafenib) are in various stages of clinical testing. These agents are producing remarkable results for patients, but are also presenting new challenges. Clinical toxicities and drug resistance are topmost issues. Some of the most common and vivid representations of adverse events to these agents are the dermatologic manifestations. Published trials and initial observations reflect a toxicity profile (e.g. squamous cell carcinomas/keratoacanthomas, maculopapular rashes, hyperkeratosis) that is distinct from cutaneous toxicities from EGFR and mTOR inhibitors (acneiform rash, paronychia, xerosis). Their management extends beyond conservative treatment and includes specific physical and surgical treatment modalities, skill sets unique to dermatologists. All these pose significant challenges to clinicians, and sound knowledge of such toxicities and their management will likely result in improved patient outcomes and quality of life. In this manuscript, we provide an overview of the emerging scientific literature on dermatological adverse events arising out of BRAF inhibition.
authors: Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Rockefeller Outpatient Pavilion, Suite 228, 160 East 53rd St, New York, NY, 10022, USA.
authors: Viswanath Reddy
authors: VR
authors: Belum
authors: Alyssa
authors: A
authors: Fischer
authors: Jennifer Nam
authors: JN
authors: Choi
authors: Mario E
authors: ME
authors: Lacouture
mesh_terms: D003875:Drug Eruptions; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009154:Mutation; D010212:Papilloma / Q000139:chemically induced; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000276:immunology; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf