Abstract ED02-03: Animal models for human pancreatic cancer prevention

Abstract

Abstract Pancreatic cancer has the worst prognosis and is the fourth leading cause of cancer-related deaths in the United States. The five-year survival for this disease is <6% and it is lethal to almost all of the patients diagnosed. As with many epithelial cancers, pre-invasive precursors in the pancreas progress slowly over many years to decades to development of invasive pancreatic cancers in humans. Lack of early detection and effective interventions are major factors contributing to the poor prognosis and dismal survival rates of pancreatic cancer patients for more than sixty years. Detection of pancreatic cancer at an early stage might permit life-saving interventions. Use of tumor xenografts and/or orthotopic models to predict valid targets and for design and development of drugs for pancreatic cancer patients has been disappointing. Animal models with etiological relevance that recapitulate the molecular pathology of human pancreatic intraepithelial neoplasia (PanINs) and their progression to pancreatic ductal adenocarcinoma (PDAC) are ideal models for establishing pancreatic cancer prevention and treatment strategies. Recent advent in genetically engineered mouse (GEM) models, such as development of transgenic KrasG12D-dependent mouse models of PDAC, that mimic human PDAC offer opportunities to identify putative targets of pancreatic lesion development and targeted drug strategies for PDAC prevention. We will present recent advances on i) selection of optimal Kras mouse models for prevention and early diagnosis, and ii) application of Whole Transcriptome (SOLiD) approaches to identify druggable targets for PanINs and PDAC. Then, iii) we will provide a few examples of development of molecularly targeted chemopreventive drugs using the krasG12D mouse model. Citation Format: Chinthalapally V. Rao. Animal models for human pancreatic cancer prevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED02-03.