Mechanisms of skin aging induced by EGFR inhibitors Journal Article
| Authors: | Gerber, P. A.; Buhren, B. A.; Schrumpf, H.; Hevezi, P.; Bölke, E.; Sohn, D.; Jänicke, R. U.; Belum, V. R.; Robert, C.; Lacouture, M. E.; Homey, B. |
| Article Title: | Mechanisms of skin aging induced by EGFR inhibitors |
| Abstract: | 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. © 2016, Springer-Verlag Berlin Heidelberg. |
| Keywords: | erlotinib; aging; targeted therapy; senescence; egfr |
| Journal Title: | Supportive Care in Cancer |
| Volume: | 24 |
| Issue: | 10 |
| ISSN: | 0941-4355 |
| Publisher: | Springer Verlag |
| Date Published: | 2016-10-01 |
| Start Page: | 4241 |
| End Page: | 4248 |
| Language: | English |
| DOI: | 10.1007/s00520-016-3254-7 |
| PROVIDER: | scopus |
| PUBMED: | 27165055 |
| PMCID: | PMC5611667 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2016 -- Source: Scopus |
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