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Effects of epidermal growth factor receptor and insulin‐like growth factor 1 receptor inhibition on proliferation and intracellular signaling in cutaneous SCCHN: Potential for dual inhibition as a therapeutic modality
Author(s) -
Clayburgh Daniel R.,
Gross Neil D.,
Proby Charlotte,
Koide Jade,
Wong Melissa H.
Publication year - 2013
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.22936
Subject(s) - epidermal growth factor receptor , erlotinib , cancer research , growth factor receptor inhibitor , egfr inhibitors , mapk/erk pathway , protein kinase b , growth factor receptor , cell growth , epidermal growth factor , growth inhibition , insulin like growth factor receptor , head and neck squamous cell carcinoma , growth factor , receptor , insulin like growth factor 1 receptor , erbb3 , signal transduction , biology , medicine , cancer , microbiology and biotechnology , head and neck cancer , biochemistry
Background Combined inhibition of epidermal growth factor receptor (EGFR) and insulin‐like growth factor‐1 receptor (IGF‐1R) has been proposed as a therapy for cutaneous squamous cell carcinoma of the head and neck (SCCHN). Methods Receptor expression and downstream signaling were assessed in cutaneous squamous cell carcinoma (SCC) cell lines and patient samples. EGFR and IGF‐1R signaling was inhibited in cutaneous SCC cell lines using erlotinib and/or picropodophyllin. Results EGFR and IGF‐1R were overexpressed in cutaneous SCCHN specimens relative to normal skin. Dual inhibition of both receptors prevented cell growth and decreased activation of Akt and p42/44 mitogen‐activated protein kinase (MAPK) more effectively than either inhibitor alone. Conclusion Dual inhibition of EGFR and IGF‐1R is effective at blocking cell growth, and is correlated with inhibition of Akt and p42/44 MAPK, suggesting that this may be a promising treatment for cutaneous SCCHN. © 2012 Wiley Periodicals, Inc. Head Neck, 2013