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Mechanisms of skin aging induced by EGFR inhibitors

Peter Arne Gerber1, Bettina Alexandra Buhren2, Holger Schrumpf2

  • 1Department of Dermatology, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, D-40225, Duesseldorf, Germany. peterarne.gerber@med.uni-duesseldorf.de.

Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer
|May 12, 2016
PubMed
Abstract

Insights

Epidermal Growth Factor Receptor (EGFR) inhibition accelerates skin aging by altering keratinocyte function. This study investigated the molecular mechanisms behind these aging-like skin changes observed in patients.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Oncology

Background:

  • The precise mechanisms driving skin aging remain incompletely understood.
  • Anecdotal evidence suggests that inhibiting the Epidermal Growth Factor Receptor (EGFR) may accelerate skin aging.
  • This study investigates the link between EGFR inhibition and aging-like skin changes.

Purpose of the Study:

  • To clinically characterize skin changes associated with Epidermal Growth Factor Receptor Inhibitor (EGFRIs) use.
  • To explore the cellular and molecular mechanisms underlying these treatment-induced skin alterations.
  • To compare EGFR expression in young versus aged skin.

Main Methods:

  • Analysis of patients undergoing prolonged EGFRIs treatment for aging-like skin changes.
  • In vitro study of primary human keratinocytes treated with erlotinib.
  • Assessment of extracellular matrix regulation, senescence markers, and cell cycle status.
  • Comparison of baseline EGFR expression in young (<25 years) and aged (>65 years) skin.

Main Results:

  • 12 patients exhibited progressive aging signs: xerosis cutis, atrophy, rhytide formation, and actinic purpura.
  • Erlotinib treatment in keratinocytes led to decreased hyaluronan synthases (HAS2, HAS3).
  • Senescence-associated genes (p21, p53, IL-6, maspin) were upregulated, with G1 cell cycle arrest and increased SA β-Gal activity.
  • Aged skin showed significantly lower baseline EGFR density compared to young skin.

Conclusions:

  • EGFR inhibition induces molecular changes in keratinocytes.
  • These alterations likely contribute to the observed skin aging in patients receiving EGFRIs.
  • Findings provide insight into the pathogenesis of treatment-related skin aging.
Keywords:
AgingEGFRErlotinibSenescenceTargeted therapy

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