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.

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.