Mechanisms underlying skin disorders induced by EGFR inhibitors

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is frequently mutated or overexpressed in a large number of tumors such as carcinomas or glioblastoma. Inhibitors of EGFR activation have been successfully established for the therapy of some cancers and are more and more frequently being used as first or later line therapies. Although the side effects induced by inhibitors of EGFR are less severe than those observed with classic cytotoxic chemotherapy and can usually be handled by out-patient care, they may still be a cause for dose reduction or discontinuation of treatment that can reduce the effectiveness of antitumor therapy. The mechanisms underlying these cutaneous side effects are only partly understood. Important questions, such as the reasons for the correlation between the intensity of the side effects and the efficiency of treatment with EGFR inhibitors, remain to be answered. Optimized adjuvant strategies to accompany anti-EGFR therapy need to be found for optimal therapeutic application and improved quality of life of patients. Here, we summarize current literature on the molecular and cellular mechanisms underlying the cutaneous side effects induced by EGFR inhibitors and provide evidence that keratinocytes are probably the optimal targets for adjuvant therapy aimed at alleviating skin toxicities.