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Updated: May 22, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signalling pathway and their management

I Manousaridis1, S Mavridou, S Goerdt

  • 1Department of Dermatology, Venereology and Allergology, University Medical Centre Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.

Journal of the European Academy of Dermatology and Venereology : JEADV
|May 1, 2012
PubMed

Insights

Targeted cancer therapies inhibiting the RAS-RAF-MEK-ERK pathway can cause skin toxicities. Early detection and management of these side effects, including potential skin tumors, are crucial for patient care.

Area of Science:

  • Oncology
  • Dermatology
  • Pharmacology

Background:

  • Mutations in the RAS-RAF-MEK-ERK pathway are implicated in various cancers, including melanoma and carcinomas.
  • Targeted inhibitors of this pathway are under clinical investigation for antitumor potential.
  • Vemurafenib is an approved drug in this class for advanced melanoma.

Purpose of the Study:

  • To review published data on cutaneous side effects associated with RAS-RAF-MEK-ERK pathway inhibitors.
  • To provide clinicians with guidance on managing these treatment-induced skin toxicities.
  • To highlight the importance of early detection of therapy-induced epithelial skin tumors.

Main Methods:

  • Systematic review of clinical trial results and case series.
  • Analysis of reported cutaneous adverse events.
  • Compilation of management strategies for skin toxicities.

Main Results:

  • RAS-RAF-MEK-ERK pathway inhibitors are associated with a distinct profile of cutaneous toxicities, similar to EGFR and multikinase inhibitors.
  • Common side effects include exanthema, palmar-plantar erythrodysesthesia, hyperkeratosis, xerosis, pruritus, photosensitivity, and paronychia.
  • Therapy can induce epithelial skin tumors, particularly keratoacanthomas, necessitating vigilant monitoring.

Conclusions:

  • While generally safe, RAS-RAF-MEK-ERK pathway inhibitors can cause significant skin toxicities that are often manageable with conservative treatments.
  • Early recognition and management of these side effects are essential.
  • Close monitoring for the development of secondary skin malignancies is critical during treatment.

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