Autochthonous Mouse Models of Cancer: Development and Use in Therapeutic Screens

人类癌症的小鼠模型对于我们理解癌症的生物学， 以及它的治疗。在这个项目中，我们描述了四种上皮细胞的小鼠模型的进一步发展， 肿瘤类型，结肠、子宫颈、胰腺和乳腺的肿瘤类型，以及它们在筛选新的治疗药物中的用途 在以前的项目中发现的药物。将使用的小鼠模型已经开发和/或 由共同项目负责人Dove（结肠），Lambert（宫颈），Sandgren（胰腺）， 亚历山大（乳房）和莫泽（结肠和乳房）。这些小鼠模型将在上下文中进一步完善 使它们更适合用于治疗筛选。这 发展工作将包括继续评估和改进肿瘤成像能力， 允许在用候选治疗剂治疗动物之前、期间和之后对肿瘤进行真实的时间成像 毒品肿瘤成像工作将与Jamey Weichert博士密切合作， 在威斯康星州大学综合癌症中心的小动物成像。一旦模型 经全面完善后，将用于筛选在项目1下产生的若干候选药物 和2个已经通过基于组织培养的细胞毒性和基于动物的药物动力学筛选。这 药物筛选将与核心C一起进行。我们不仅要测试药物在降低 肿瘤负荷，而且还表征药物治疗对多个参数的组织病理学影响， 不同的癌症类型，并决定药物预防复发的能力。

Mouse models for human cancer have been crucial to our understanding of the biology of cancer, its origins and its treatment. In this project, we describe the further development of mouse models for four epithelial tumor types, that of the colon, cervix, pancreas and breast and their use in screening novel therapeutic drugs discovered in the prior projects. The mouse models that will be used have been developed and/or characterized 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 context of the proposed studies to make them more amenable to theier use in therapeutic screens. This developmental effort will include continued assessment and refinement of tumor imaging capabilities that will allow for real time imaging of tumors before, during and after treatment of animals with candidate therapeutic drugs. The tumor imaging effort will be pursued in close collaboration with Dr. Jamey Weichert, an expert in small animal imaging here at the University of Wisconsin Comprehensive Cancer Center. Once the models are fully refined, they will be used to screen a select number of candidate drugs generated under Projects 1 and 2 that have passed tissue culture based cytotoxicity and animal based pharmakinetics screens. This drug screening will be performed together with Core C. We will not only test the efficacy of drugs in reducing tumor burden, but also characterize the histopathological effects of drug treatment on multiple parameters of the different cancer types and determine the ability of the drugs to prevent recurrence.