Mouse models for human cancer have been crucial to our understanding of the biology of cancer, its originsand its treatment. In this project, we describe the further development of mouse models for four epithelialtumor types, that of the colon, cervix, pancreas and breast and their use in screening novel therapeuticdrugs discovered in the prior projects. The mouse models that will be used have been developed and/orcharacterized by the co-project leaders, Drs. Dove (colon), Lambert (cervix), Sandgren (pancreas),Alexander (breast) and Moser (colon and breast). These mouse models will be further refined in the contextof the proposed studies to make them more amenable to theier use in therapeutic screens. Thisdevelopmental effort will include continued assessment and refinement of tumor imaging capabilities that willallow for real time imaging of tumors before, during and after treatment of animals with candidate therapeuticdrugs. The tumor imaging effort will be pursued in close collaboration with Dr. Jamey Weichert, an expert insmall animal imaging here at the University of Wisconsin Comprehensive Cancer Center. Once the modelsare fully refined, they will be used to screen a select number of candidate drugs generated under Projects 1and 2 that have passed tissue culture based cytotoxicity and animal based pharmakinetics screens. Thisdrug screening will be performed together with Core C. We will not only test the efficacy of drugs in reducingtumor burden, but also characterize the histopathological effects of drug treatment on multiple parameters ofthe different cancer types and determine the ability of the drugs to prevent recurrence.
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