EGFR-directed therapies to treat non-small-cell lung cancer.

Lung cancer is the leading cause of cancer death in men and women. In 2008, in the US > 200,000 patients were diagnosed with lung cancer and > 160,000 died from their disease. Over 80% of lung cancers are of the non-small cell type, for which chemotherapy has demonstrated modest survival benefits at all stages of disease. Agents that alter critical molecular cell growth pathways are a growing area of research and development including targeted therapies directed at the EGFR. Downstream effects of EGFR dimerization and activation include cell proliferation, differentiation and angiogenesis, key events in the malignant process. Two main classes of drugs have been developed, small molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies directed against the extracellular domain of the receptor. This review discusses clinical studies with several new therapies and the plans for drug development.