Targeting EGFR and HER-2 receptor tyrosine kinases for cancer drug discovery and development

Conventional anticancer therapy using cytotoxic drugs lacks selectivity and is prone to toxicity and drug resistance. Anticancer therapies targeting aberrant growth factor receptor signaling are gaining interest. The erbB receptor family belongs to the type I, the receptor tyrosine kinases class, and comprises EGFR, HER-2, HER-3, and HER-4. It has been targeted for solid tumor therapy, including breast, ovarian, colon, head-and-neck, and non-small-cell lung cancers. This review summarizes structural aspects of this class of growth factor receptors, their oncogenic expression, and various pharmacological interventions including biological products and small molecules that inhibit these enzymes. We have also discussed various mutations that occur in EGFR and their consequences on anticancer therapy. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 5, 569–594, 2006