Background: Salivary gland malignancies represent 1-2% of human head and neck cancers with approximately 3,300 new cases per year in the United States. Surgery is the best treatment, however must tumors are too advanced at discovery and are unresectable. Furthermore, many surgeries are not margin negative and thus they recur. In addition, advanced tumors metastasize, which makes them fatal. The lack of research tools and the limited number of cases per year makes it difficult for investigators to study the development and progression of these tumors. The aim of this study was to characterize a novel inducible mouse model of salivary gland tumors, which develops by the activation of oncogenic K-RasG12V. Methods: We developed transgenic mice with Cre regulated mutant K-RasG12D and a specific tamoxifen regulated Cre (Ela-CreER). Double transgenic animals and littermate controls were treated with tamoxifen over 3 consecutive days and after 3, 8, and 15 days they were sacrificed and analyzed histologically. Results: Tamoxifen fed animals with mutant K-RasG12D expression in the salivary gland develop tumors with intense fibrosis and inflammatory cell infiltration. Histologically the tumors resembled human high grade salivary sarcomas. Conclusions: Our results show the development of a new animal model to study the role of K-Ras in the progression of salivary gland tumors and could be a useful tool for future salivary gland tumor studies. In particular it should serve as a useful preclinical model to test for drugs against inflammatory response pathways induced by activated K-RasG12V in salivary gland tumors.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2357. doi:1538-7445.AM2012-2357