We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Mechanisms of skin aging induced by EGFR inhibitors.
- Authors
Gerber, Peter; Buhren, Bettina; Schrumpf, Holger; Hevezi, Peter; Bölke, Edwin; Sohn, Dennis; Jänicke, Reiner; Belum, Viswanath; Robert, Caroline; Lacouture, Mario; Homey, Bernhard; Gerber, Peter Arne; Buhren, Bettina Alexandra; Jänicke, Reiner U; Belum, Viswanath Reddy; Lacouture, Mario E
- Abstract
<bold>Background: </bold>The mechanisms of skin aging have not been completely elucidated. Anecdotal data suggests that EGFR inhibition accelerates aging-like skin changes.<bold>Objective: </bold>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.<bold>Patients and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>EGFR inhibition results in molecular alterations in keratinocytes that may contribute to the observed skin aging of patients treated with respective targeted agents.
- Subjects
ERLOTINIB; AGING; EXTRACELLULAR matrix; KERATINOCYTES; HYALURONIC acid; EPIDERMAL growth factor; RESEARCH funding; SKIN aging; SKIN diseases; RETROSPECTIVE studies; CHEMICAL inhibitors
- Publication
Supportive Care in Cancer, 2016, Vol 24, Issue 10, p4241
- ISSN
0941-4355
- Publication type
journal article
- DOI
10.1007/s00520-016-3254-7