Abstract A101: Dose-related suppression of rat oral carcinogenesis by the EGF receptor-tyrosine kinase inhibitor, gefitinib

Activation of the epidermal growth factor receptor (EGFR) stimulates signal transduction pathways that regulate cell proliferation and may be causally involved in carcinogenesis. Recent data suggest that EGFR expression is a predictive biomarker for the risk of oral cancer in humans, and that alterations in EGFR expression or action may be directly involved in oral carcinogenesis. Gefitinib (N-(3-chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)-quinazolin-4-amine; ZD1839; Iressa) is a specific inhibitor of EGFR tyrosine kinase (EGFR-TK). The present study was performed to evaluate the activity of gefitinib as an inhibitor of oral cancer induction in rats. Squamous cell carcinomas of the tongue were induced in male F344 rats by drinking water administration of 4-nitroquinoline-1-oxide (NQO; 20 ppm for 10 weeks). After NQO administration was completed, rats were randomized into groups of 25 and received [a] unsupplemented basal diet only (dietary control); [b] basal diet + gefinitib (50 mg/kg diet); or [c] basal diet + gefinitib (100 mg/kg diet). All diets were fed continuously from week 10 until the end of the study at week 26. Dietary administration of gefinitib induced a dose-related inhibition of oral cancer induction (cancer incidences of 57% and 36% in low and high dose groups, respectively, versus 80% incidence in the dietary control group; p Citation Information: Cancer Prev Res 2010;3(12 Suppl):A101.