Monoclonal Antibodies to Target Epidermal Growth Factor Receptor-Positive Tumors: A New Paradigm for Cancer Therapy

Cancer. 2002 Mar 1;94(5):1593-611. doi: 10.1002/cncr.10372.

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-alpha, 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.

MeSH terms

  • Antibodies, Monoclonal*
  • Combined Modality Therapy
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / immunology*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ligands
  • Neoplasms / drug therapy
  • Neoplasms / immunology

Substances

  • Antibodies, Monoclonal
  • Ligands
  • ErbB Receptors