Animal Models for the Study of Human Disease

In humans, the natural history of prostate cancer spans 30–40 years, which makes it a difficult disease to model in rodents. Furthermore, the molecular pathology of prostate cancer responsible for tumor initiation and progression is complex and often redundant. The sequential changes in oncogene and tumor suppressor gene expression during prostate cancer progression have not been fully delineated. Despite these issues, there are model systems, including carefully designed orthotopic xenograft models, that provide robust platforms for drug evaluation and studying the effects of diet and environmental stress on prostate carcinogenesis. Comprehensive transgenic and knockout models have also been developed that recapitulate individual steps in tumor initiation and metastatic progression and highlight the importance of the tumor microenvironment. While very few of the transgenic and knockout systems recapitulate the entire natural history of prostate cancer, individual model systems provide valuable genetic insight into the biological consequences of disrupting prostate homeostasis.