TY - JOUR
T1 - Mechanisms of skin aging induced by EGFR inhibitors
AU - Gerber, Peter Arne
AU - Buhren, Bettina Alexandra
AU - Schrumpf, Holger
AU - Hevezi, Peter
AU - Bölke, Edwin
AU - Sohn, Dennis
AU - Jänicke, Reiner U.
AU - Belum, Viswanath Reddy
AU - Robert, Caroline
AU - Lacouture, Mario E.
AU - Homey, Bernhard
N1 - Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - Aging
KW - EGFR
KW - Erlotinib
KW - Senescence
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=84966577726&partnerID=8YFLogxK
U2 - 10.1007/s00520-016-3254-7
DO - 10.1007/s00520-016-3254-7
M3 - Article
C2 - 27165055
AN - SCOPUS:84966577726
SN - 0941-4355
VL - 24
SP - 4241
EP - 4248
JO - Supportive Care in Cancer
JF - Supportive Care in Cancer
IS - 10
ER -