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Archives of Toxicology

, Volume 88, Issue 6, pp 1189–1203 | Cite as

Epidermal growth factor receptor signalling in keratinocyte biology: implications for skin toxicity of tyrosine kinase inhibitors

  • Saveria Pastore
  • Daniela Lulli
  • Giampiero Girolomoni
Review Article

Abstract

The epidermal growth factor receptor (EGFR) and its ligands have been long recognized as centrally involved in the growth and repair process of epithelia, as well as in carcinogenesis. In addition, the EGFR has been demonstrated to be importantly involved in the control of inflammatory responses. During this last decade, a number of highly specific agents targeting this system have become an integral component of pharmacologic strategies against many solid malignancies. These drugs have led to increased patient survival and made therapy more tolerant when compared to conventional cytotoxic drugs. Nonetheless, their use is associated with a constellation of toxic effects on the skin, including follicular pustules, persistent inflammation, xerosis and pruritus, and enhanced susceptibility to infections. This dramatic impairment of skin homoeostasis underscores the centrality of the EGFR–ligand system in the whole skin immune system. So far, no mechanism-based approaches are available to specifically counteract the adverse effects of anti-EGFR drugs or any other class of tyrosine kinase inhibitors. Only the knowledge of the cellular and molecular events underlying these adverse effects in humans, combined with in vitro/in vivo models able to mimic these toxic responses, may guide the development of mechanism-based treatment or prevention strategies.

Keywords

Epidermal growth factor inhibitor Tyrosine kinase inhibitor Skin inflammation Antimicrobial peptide Cytokine Chemokine 

Notes

Conflict of interest

G. Girolomoni has received advisory/speaker honoraria and/or research funding from AbbVie, Actelion, Almirall, Boehringer Ingelheim, Celgene, Dompè, Eli-Lilly, Galderma, GSK, Janssen, Leo Pharma, Merck-Serono, Maruho, MSD, Novartis and Pfizer.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Saveria Pastore
    • 1
  • Daniela Lulli
    • 1
  • Giampiero Girolomoni
    • 2
  1. 1.Laboratory of Experimental ImmunologyIDI-IRCCSRomeItaly
  2. 2.Section of Dermatology, Department of MedicineUniversity of VeronaVeronaItaly

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