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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

Authors

  • Daniel R. Clayburgh MD, PhD,

    Corresponding author
    1. Department of Otolaryngology – Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon
    • Department of Otolaryngology, Head and Neck Surgery, Oregon Health and Science University Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Mailcode L468R, Portland, OR 97239
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  • Neil D. Gross MD,

    1. Department of Otolaryngology – Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon
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  • Charlotte Proby PhD,

    1. School of Medicine, University of Dundee, Dundee, Scotland
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  • Jade Koide BS,

    1. School of Medicine, Oregon Health and Science University, Portland, Oregon
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  • Melissa H. Wong PhD

    Corresponding author
    1. Department of Dermatology, Oregon Health and Science University, Portland, Oregon
    • Department of Dermatology, Oregon Health and Science University Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Mailcode L468R, Portland, OR 97239
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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. © 2012 Wiley Periodicals, Inc. Head Neck, 2013

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