Epidermal growth factor receptor tyrosine kinase inhibitors in cancer therapy

Receptor tyrosine kinases are transmembrane proteins involved in signal transduction. They propagate growth factor signals from the cell surface to intracellular processes that control critical functions such as growth, differentiation, angiogenesis and inhibition of apoptosis. In malignancies, these signaling pathways are often exploited to optimize tumor growth and metastasis. One such family of receptor tyrosine kinases is the epidermal growth factor receptor (EGFR) tyrosine kinase. These receptors are overexpressed in a wide variety of epithelial cancers and have been implicated in tumor aggressiveness. Thus, targeting the EGFR tyrosine kinase has attracted considerable attention. This review will summarize current preclinical and clinical knowledge of the small-molecule oral inhibitors of the EGFR tyrosine kinase, which include ZD-1839, OSI-774, CI-1033, EKB-569, PKI-166, GW-2016 and BIBX-1382.