Blockade of epidermal growth factor receptor (EGFR) activity

The rapidly expanding knowledge of the pathogenesis of cancer at the molecular level is providing new targets for drug discovery and development. The key role that EGFR plays in the intracellular transduction of environmental variations and the maintenance of cellular homeostasis explains the dependence that many tumor types have on this pathway, and the pivotal role that it plays in the development of malignant features such as uncontrolled proliferation, augmented invasion, and the ability to escape apoptosis. An enormous body of knowledge has been gathered in the past 20 years that has enabled the development of rationally designed EGFR-targeted therapies, and the results of their clinical evaluation are now becoming available. The lack of positive results of some of these trials has highlighted the need for a robust preclinical knowledge in order to efficiently select patients for therapy, and have prompted the implementation of novel trial designs with rational endpoints. (c) 2004 Elsevier Ireland Ltd. All rights reserved.