New targeted therapies for non-small-cell lung cancer: a focus on the epidermal growth factor receptor.

Advances in chemotherapy and multimodality treatments of patients with non-small-cell lung cancer (NSCLC) have improved outcomes for these patients over the past decade. Unfortunately, gains have been modest, and new therapeutic strategies are eagerly awaited. Therapies that target receptors vital to the proliferation and survival of cancer cells are particularly attractive areas of research. The epidermal growth factor receptor (EGFR) is widely expressed in NSCLC. Preclinical studies demonstrate that inhibition of EGFR using antibodies or tyrosine kinase inhibitors has led to growth inhibition and tumor regression in a variety of models. A number of agents are currently in clinical trials; the most information in NSCLC is currently available on the tyrosine kinase inhibitors. Phase II trials involving patients with advanced NSCLC and whose disease is progressive after chemotherapy have demonstrated clear clinical benefit. Studies are ongoing, integrating EGFR-targeted therapy with chemotherapy and radiation in patients with earlier stage NSCLC, as well as in chemoprevention. In all of these settings, a further understanding of the biology of EGFR in relationship to other cellular events will be critical in optimizing therapeutic approaches with these novel agents.