Monoclonal antibodies targeting the epidermal growth factor receptor

R. Bianco, G. Daniele, F. Ciardiello, G. Tortora

Research output: Contribution to journalArticlepeer-review

Abstract

The epidermal growth factor receptor (EGFR, HER1) autocrine pathway contributes to a number of highly relevant processes in cancer development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis and metastatic spread. The crucial role that EGFR plays in human cancers has led to an extensive search for selective inhibitors of its signaling pathway. The results of a large body of preclinical studies and clinical trials thus far conducted suggest that targeting the EGFR could bring a significant contribution to cancer therapy. A variety of different approaches are currently being used to target the EGFR. The most promising strategies in clinical development include monoclonal antibodies, to prevent ligand binding, and small molecules inhibitors of the tyrosine kinase enzymatic activity, that inhibit autophosphorylation and downstream intracellular signaling. Several blocking monoclonal antibodies against the EGFR have been developed. Among these, IMC-225 is a chimeric human-mouse monoclonal IgG1 antibody that has been the first anti-EGFR targeted therapy to enter clinical evaluation in cancer patients in Phase II and III studies, alone or in combination with conventional radiotherapy and chemotherapy. However, other antibodies against EGFR have demonstrated antitumor activity in several preclinical models of human cancer and are currently under investigation in the clinical setting, such as ICR62, ABX-EGF and EMD72000. This review will focus on all the preclinical data available on monoclonal antibodies engineered against the EGF receptor.

Original languageEnglish
Pages (from-to)275-287
Number of pages13
JournalCurrent Drug Targets
Volume6
Issue number3
DOIs
Publication statusPublished - May 2005

Keywords

  • Cetuximab
  • Chemotherapy
  • EGFR
  • Monoclonal antibodies
  • Radiotherapy
  • TGFα

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

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