Dermatological adverse events from BRAF inhibitors: a growing problem

Curr Oncol Rep. 2013 Jun;15(3):249-59. doi: 10.1007/s11912-013-0308-6.

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.

Publication types

  • Review

MeSH terms

  • Drug Eruptions
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Indoles / adverse effects*
  • Indoles / therapeutic use
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / immunology
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / pathology
  • Mutation
  • Papilloma / chemically induced
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / immunology
  • Risk Assessment
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Sulfonamides / adverse effects*
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Vemurafenib

Substances

  • Indoles
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf