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

Daniel Clayburgh, Neil D. Gross, Charlotte Proby, Jade Koide, Melissa Wong

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)86-93
Number of pages8
JournalHead and Neck
Volume35
Issue number1
DOIs
StatePublished - Jan 2013

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Somatomedin Receptors
Epidermal Growth Factor Receptor
Skin
Mitogen-Activated Protein Kinase 1
Squamous Cell Carcinoma
Therapeutics
Cell Line
Growth
Carcinoma, squamous cell of head and neck

Keywords

  • cutaneous squamous cell carcinoma
  • epidermal growth factor receptor
  • insulin-like growth factor receptor

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

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title = "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",
abstract = "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.",
keywords = "cutaneous squamous cell carcinoma, epidermal growth factor receptor, insulin-like growth factor receptor",
author = "Daniel Clayburgh and Gross, {Neil D.} and Charlotte Proby and Jade Koide and Melissa Wong",
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TY - JOUR

T1 - Effects of epidermal growth factor receptor and insulin-like growth factor 1 receptor inhibition on proliferation and intracellular signaling in cutaneous SCCHN

T2 - Potential for dual inhibition as a therapeutic modality

AU - Clayburgh, Daniel

AU - Gross, Neil D.

AU - Proby, Charlotte

AU - Koide, Jade

AU - Wong, Melissa

PY - 2013/1

Y1 - 2013/1

N2 - 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.

AB - 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.

KW - cutaneous squamous cell carcinoma

KW - epidermal growth factor receptor

KW - insulin-like growth factor receptor

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