Dermatological Adverse Events from BRAF Inhibitors: A Growing Problem
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PALLIATIVE MEDICINE (A JATOI, SECTION EDITOR)
Dermatological Adverse Events from BRAF Inhibitors: A Growing Problem Viswanath Reddy Belum & Alyssa Fischer & Jennifer Nam Choi & Mario E. Lacouture
Published online: 6 March 2013 # Springer Science+Business Media New York 2013
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.
Keywords Dermatologic . Vemurafenib . Dabrafenib . Sorafenib . BRAF inhibition . wt-BRAF . Squamoproliferative . Papilloma . Verrucous keratoses . Verruca . SCC . Keratoacanthoma . Rash . Hand foot skin reaction . Alopecia . Photosensitivity . Pruritus . Melanocytic proliferations
Introduction In recent years, there has been an increase in the development of agents targeting oncogenic pathways integral to cancer cell proliferation, tumor growth and metastasis. The detection of mutations in the RAS-RAF-MEK-ERK pathway in various cancers has generated high interest, especially with BRAF mutations in melanomas. The drugs developed towards this target have significantly improved survival in cancer patients. However, these impressive results have also been accompanied by unique challenges for the oncologist making clinical decisions. Among them, dermatological adverse events are one of the most noteworthy consequences.
Overview of MAPK Pathway V. R. Belum : A. Fischer : M. E. Lacouture (*) Dermatology Service, Department of Medicine, Memorial SloanKettering Cancer Center, Rockefeller Outpatient Pavilion, Suite 228, 160 East 53rd St, New York, NY 10022, USA e-mail: [email protected] J. N. Choi Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA
The intracellular mitogen-activated protein kinase (MAPK) pathway, also known as the ‘RAS-RAF-MEK-ERK pathway’, is a seque
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