Mechanisms of skin aging induced by EGFR inhibitors

Peter Arne Gerber, Bettina Alexandra Buhren, Holger Schrumpf, Peter Hevezi, Edwin Bölke, Dennis Sohn, Reiner U. Jänicke, Viswanath Reddy Belum, Caroline Robert, Mario E. Lacouture, Bernhard Homey

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    Résumé

    Background: The mechanisms of skin aging have not been completely elucidated. Anecdotal data suggests that EGFR inhibition accelerates aging-like skin changes. Objective: The objective of the study was to evaluate the clinical characteristics and investigate the cellular and molecular mechanisms underlying skin changes associated with the use of EFGRIs. Patients and methods: Patients during prolonged treatment with EGFRIs (>3 months) were analyzed for aging-like skin changes. Baseline EGFR expression was compared in young (<25 years old) vs. old (> 65 years old) skin. In addition, the regulation of extracellular matrix, senescence-associated genes, and cell cycle status was measured in primary human keratinocytes treated with erlotinib in vitro. Results: There were progressive signs of skin aging, including xerosis cutis, atrophy, rhytide formation, and/or actinic purpura in 12 patients. Keratinocytes treated with erlotinib in vitro showed a significant down-modulation of hyaluronan synthases (HAS2 and HAS3), whereas senescence-associated genes (p21, p53, IL-6, maspin) were upregulated, along with a G1 cell cycle arrest and stronger SA β-Gal activity. There was significantly decreased baseline expression in EGFR density in aged skin, when compared to young controls. Conclusions: EGFR inhibition results in molecular alterations in keratinocytes that may contribute to the observed skin aging of patients treated with respective targeted agents.

    langue originaleAnglais
    Pages (de - à)4241-4248
    Nombre de pages8
    journalSupportive Care in Cancer
    Volume24
    Numéro de publication10
    Les DOIs
    étatPublié - 1 oct. 2016

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