Monoclonal antibodies to target epidermal growth factor receptor–positive tumors: A new paradigm for cancer therapy

Abstract

BACKGROUND: Traditional cytotoxic approaches to tumor management are associated with efficacy and toxicity limitations. Blockade of the epidermal growth factor receptor (EGFR) and its ligands is a novel approach to the treatment of human tumors that offers a noncytotoxic alternative to cancer treatment. METHODS: An English‐language literature search was conducted to identify studies assessing the in vitro and in vivo effects of EGFR blockade with an emphasis on approaches that use monoclonal antibody therapy. RESULTS: The EGF pathway regulates normal cellular processes and appears to be correlated with the development of malignancy. Approximately 30% of human tumors express EGFR, which has been reported to be correlated with poor prognosis and diminished disease‐free and overall survival in selected tumor types. A number of anti‐EGFR monoclonal antibodies have been developed, which currently are undergoing clinical trials in humans. Effective anti‐EGFR monoclonal antibodies compete with endogenous ligands, primarily EGF and transforming growth factor–α, for receptor ligand‐binding sites. Binding to EGFR blocks critical signaling pathways and interferes with the growth of tumors expressing EGFR. Anti‐EGFR monoclonal antibodies that currently are under study include IMC‐C225, EMD 55900, ICR 62, and ABX‐EGF. CONCLUSIONS: These antibodies have demonstrated promising results and appear to have been well tolerated. EGFR‐targeted therapy addresses important, unmet needs in the treatment of human tumors, particularly EGFR‐positive epithelial tumors including common malignancies of the head and neck, lung, and colon. Cancer 2002;94:1593–611. © 2002 American Cancer Society. DOI 10.1002/cncr.10372