Epidermal Growth Factor Receptor Inhibitors in Cancer Treatment

Abstract

The epidermal growth factor receptor (EGFR) is a cellular transmembrane receptor with tyrosine kinase enzymatic activity which plays a key role in human cancer. EGFR-dependent signaling is involved in cancer cell proliferation, apoptosis, angiogenesis, invasion and metastasis. Targeting the EGFR is a valuable molecular approach in cancer therapy. Several anti-EGFR drugs are in Phase III clinical development as single agent or in combination with other anticancer modalities. Cetuximab (Erbitux®), a chimeric human–mouse monoclonal immunoglobin (Ig)G1 antibody, which blocks ligand binding and functional activation of the EGFR, is currently registered in the USA, Switzerland and the European Union for the treatment of advanced, irinotecan-refractory colorectal cancer. Gefitinib, (Iressa®), a small molecule EGFR-selective inhibitor of tyrosine kinase activity which blocks EGF autophosphorylation and activation, has been the first EGFR-targeting drug to be registered in 28 countries worldwide, including the USA...