title: Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition.
abstract: From immunohistochemical and ligand-binding studies, it is known that the epidermal growth factor receptor (EGFR), a member of the erbB family of receptors, is expressed in tissues of epithelial, mesenchymal and neuronal origin and plays a major role in normal cellular processes such as proliferation, differentiation and development. EGFR is highly expressed in a number of solid tumours and its expression correlates with tumour progression, resistance to chemotherapy and a poor prognosis; it is consequently an attractive target for the rational design of novel anticancer agents. Knowledge of the role of EGFR in normal tissues will help the understanding of the adverse events associated with such agents. Studies in knockout mice and preclinical toxicology studies have shown that the major effects of inhibiting the EGFR are skin and gastrointestinal toxicities. Clinical studies with inhibitors of EGFR, such as gefitinib, cetuximab and erlotinib, have shown a favourable adverse-event profile, primarily consisting of skin and gastrointestinal toxicities, as predicted from the mechanism-based effects observed in preclinical studies.
authors.affiliation: AstraZeneca KK, Umeda Sky Building Tower East, 1-88, 1-chome, Ohyodo-nakal, Kita-ku, Osaka 531-0076, Japan. S.Yano@astrazeneca.com
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yano
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kondo
authors.forename: Motonori
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Graham
authors.initials: G
authors.lastname: Richmond
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchison
authors.forename: Alan
authors.initials: A
authors.lastname: Wakeling
authors.forename: Steven
authors.initials: S
authors.lastname: Averbuch
authors.forename: Peter
authors.initials: P
authors.lastname: Wadsworth
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D000077156:Gefitinib; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011799:Quinazolines / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib