Targeting the epidermal growth factor receptor: prognostic and clinical implications

The epidermal growth factor receptor (EGFR) has been implicated in many tumorigenic processes and is therefore a promising target for novel anticancer agents such as the EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839). Clinical trials in non-small-cell lung cancer have shown gefitinib to have encouraging antitumour activity; however, not all patients exhibit the same response. This review explores whether there are potential prognostic indicators - such as biological markers, disease characteristics, or surrogate markers that might predict the response to agents such as gefitinib. Interestingly, although expression levels of the EGFR itself do not appear to predict response to gefitinib, a number of candidate genes associated with clinical response or resistance have been identified. Various demographic factors, including performance status, gender and histology, appear to have prognostic value in some settings; however, the skin toxicity associated with EGFR-targeted agents does not appear to be predictive of response to gefitinib. (C) 2003 Elsevier Science Ltd. All rights reserved.