Growth factor receptors as targets for lung cancer therapy.

Dysregulated signal transduction of growth factor receptors contributes to the process of malignant transformation by promoting cell proliferation, motility, and invasion through extracellular matrix as well as angiogenesis. Epidermal growth factor receptors (EGFR), and to a lesser extent HER2/neu, is overexpressed in the majority of nonsmall cell lung cancer (NSCLC) compared with normal tissue, making them ideal targets for the development of novel therapeutics for this disease. Multiple clinical trials have demonstrated that antireceptor strategies employing antagonistic monoclonal antibodies or low molecular weight tyrosine kinase inhibitors against EGFR are well tolerated and occasionally result in objective clinical responses in patients with advanced NSCLC. This report provides an overview of the molecular basis and the preclinical evidence supporting clinical development of anti-EGFR therapy as well as results of phase I-III clinical trials of these compounds in treating patients with solid tumors including NSCLC.