title: Mechanisms of skin aging induced by EGFR inhibitors.
abstract: The mechanisms of skin aging have not been completely elucidated. Anecdotal data suggests that EGFR inhibition accelerates aging-like skin changes.
  
  
  
  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 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.
  
  
  
  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.
  
  
  
  EGFR inhibition results in molecular alterations in keratinocytes that may contribute to the observed skin aging of patients treated with respective targeted agents.
authors.affiliation: Department of Dermatology, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, D-40225, Duesseldorf, Germany. peterarne.gerber@med.uni-duesseldorf.de.
authors.forename: Peter Arne
authors.initials: PA
authors.lastname: Gerber
authors.affiliation: Department of Dermatology, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, D-40225, Duesseldorf, Germany.
authors.forename: Bettina Alexandra
authors.initials: BA
authors.lastname: Buhren
authors.affiliation: Department of Dermatology, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, D-40225, Duesseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schrumpf
authors.affiliation: Department of Dermatology, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, D-40225, Duesseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hevezi
authors.affiliation: Clinic and Polyclinic, Radiation Therapy and Radiooncology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Edwin
authors.initials: E
authors.lastname: Bölke
authors.affiliation: Laboratory of Molecular Radiooncology, Radiation Therapy and Radiooncology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Sohn
authors.affiliation: Laboratory of Molecular Radiooncology, Radiation Therapy and Radiooncology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Reiner U
authors.initials: RU
authors.lastname: Jänicke
authors.affiliation: Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Viswanath Reddy
authors.initials: VR
authors.lastname: Belum
authors.affiliation: Dermatology Service and Paris-Sud University, Gustave Roussy Cancer Campus, Villejuif-Paris Sud, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.affiliation: Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
authors.affiliation: Department of Dermatology, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, D-40225, Duesseldorf, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D012189:Retrospective Studies; D015595:Skin Aging / Q000235:genetics*; D012871:Skin Diseases / Q000235:genetics*
chemical_list: D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: Aging; EGFR; Erlotinib; Senescence; Targeted therapy