Epidermal growth factor receptor signaling in nonsmall cell lung cancer.

Epidermal growth factor is a 170-kd protein that binds to a specific tyrosine kinase receptor, epidermal growth factor receptor (EGFR), on the cell surface. EGFR function is dysregulated in various malignancies including nonsmall cell lung cancer (NSCLC) leading to activation of several signal transduction pathways including K-RAS, PIK3, and STAT3 and STAT5, that promote cell cycle progression, proliferation, invasion, angiogenesis, and inhibit apoptosis. EGFR overexpression is seen in a majority of cases of NSCLC, but its prognostic role is controversial. EGFR inhibitors currently undergoing clinical trials in NSCLC include monoclonal antibodies or small molecule tyrosine kinase inhibitors. The only EGFR inhibitor currently approved for the treatment of NSCLC is erlotinib, a small molecule tyrosine kinase inhibitor. Although women, nonsmokers, patients with adenocarcinoma and patients with Asian ethnicity seem to have better outcomes with erlotinib, the factors predictive for response to these agents are currently the focus of investigation.