EPIDERMAL GROWTH-FACTOR RECEPTOR (EGFR) AND EGFR MUTATIONS, FUNCTION AND POSSIBLE ROLE IN CLINICAL-TRIALS

The epidermal growth factor receptor (EGFR) is a growth factor recepto r that induces cell differentiation and proliferation upon activation through the binding of one of its ligands. The receptor is located at the cell surface, where the binding of a ligand activates a tyrosine k inase in the intracellular region of the receptor. This tyrosine kinas e phosphorylates a number of intracellular substrates that activates p athways leading to cell growth, DNA synthesis and the expression of on cogenes such as fos and jun. EGFR is thought to be involved the develo pment of cancer, as the EGFR gene is often amplified, and/or mutated i n cancer cells. In this review we will focus on: (I) the structure and function of EGFR, (II) implications of receptor/ligand coexpression a nd EGFR mutations or overexpression, (III) its effect on cancer cells, (IV) the development of the malignant phenotype and (V) the clinical aspects of therapeutic targeting of EGFR.