Interference with EGFR signaling: paradigm for improving radiation response in cancer treatment.

The introduction of biologically active agents that interfere with the epidermal growth factor receptor (EGFR) provides a promising opportunity to improve cancer treatment outcomes. Several EGFR-selective agents, such as humanized monoclonal antibodies and small molecule, orally available tyrosine kinase inhibitors have shown antitumor activity in early clinical trials in advanced cancer patients. Preclinical studies have demonstrated enhanced radiation- and chemotherapy-induced tumor cytotoxicity when EGFR antagonists are implemented. More broadly, recent clinical trials have confirmed improved survival with combinations of HER-2 (a member of the ErbB family of receptors) targeted antibodies and chemotherapy in patients with advanced breast cancer. A landmark trial combining C225 antiEGFR antibody with radiation therapy for patients with locally advanced head and neck cancer has just completed accrual. Thus, emerging rapidly are cancer treatment strategies based on an improved understanding of the specific cellular and molecular abnormalities of individual tumors.