Conflict of interest All authors have contributed to the conception and design, to the analysis and interpretation of data, to the drafting of the article. All authors have revised the manuscript critically for important intellectual content and have approved the version to be published.
Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signalling pathway and their management
Article first published online: 28 APR 2012
© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology
Journal of the European Academy of Dermatology and Venereology
Volume 27, Issue 1, pages 11–18, January 2013
How to Cite
Manousaridis, I., Mavridou, S., Goerdt, S., Leverkus, M. and Utikal, J. (2013), Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signalling pathway and their management. Journal of the European Academy of Dermatology and Venereology, 27: 11–18. doi: 10.1111/j.1468-3083.2012.04546.x
- Issue published online: 18 DEC 2012
- Article first published online: 28 APR 2012
- Received: 27 December 2011; Accepted: 26 March 2012
Mutations in genes encoding for proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of tumor entities, including malignant melanoma, thyroid, colonic and ovarian carcinomas, and some sarcomas. Thus, a number of inhibitors of this pathway have been developed, whose antitumor potential is currently being assessed in different clinical trials. Up to now one drug of this category (vemurafenib) has been approved by the FDA and the European Commission for late-stage melanoma. Although these new targeted anticancer therapies are generally considered to be safe and well tolerated, certain toxicities have been attributed to them, with cutaneous side effects being perhaps the most frequent amongst them. Based on results of clinical trials and on case series, a distinct profile of cutaneous toxicity has been observed, which is similar to that of EGFR and multikinase inhibitors. As exanthema, palmar-plantar erythrodysesthesia syndrome, hyperkeratosis, xerosis, pruritus, photosensitivity, and paronychia, can be controlled in most cases with common conservative modalities, special attention should be given to the early detection of epithelial skin tumors (mainly keratoakanthomas) that can be induced during therapy with these agents. This report reviews all current published data on cutaneous side effects of RAS-RAF-MEK-ERK pathway inhibitors, and attempts to provide the clinician with clear hints for their management.