Current and Emerging Roles of Epidermal Growth Factor Receptor Inhibitors in Advanced Non-Small Cell Lung Cancer

Recent advances in basic and translational research have elucidated important molecular alterations that underlie neoplastic transformation and progression in non-small cell lung cancer (NSCLC). Specifically, the epidermal growth factor receptor (EGFR) signal transduction pathway presents therapeutic opportunities at various levels from the extracellular ligands to the transmembrane receptor and associated intracellular tyrosine kinase and the downstream signaling molecules. Two main categories of molecular agents targeting the EGFR-associated network have been incorporated into clinical practice: monoclonal antibodies that interfere with the binding of the natural ligand to the receptor (e.g. cetuximab) or tyrosine kinase inhibitors (e.g. erlotinib, gefitinib) that inhibit the activation of receptor tyrosine kinase leading to abrogation of signal propagation. Several other EGFR-targeting agents are currently under intensive preclinical and clinical investigation. In the current review we summarize data concerning the current and emerging role of EGFR-targeting molecules in the treatment of NSCLC.