Animal models, particularly mouse models, play a central role in the study of the etiology, prevention and treatment of human prostate cancer (PCa). While tissue culture models are extremely useful in understanding the biology of PCa, they cannot recapitulate the complex cellular interactions within the tumor microenvironment that play a key role in cancer initiation and progression. The NCI Mouse Models of Human Cancers Consortium convened a group of human and veterinary pathologists to review the current animal models of PCa and make recommendations regarding the pathological analysis of these models. Over 40 different models with 439 samples were reviewed including genetically engineered mouse models, xenograft, rat and canine models. Numerous relevant models have been developed over the last 15 years and each approach has strengths and weaknesses. Analysis of multiple genetically engineered models has shown that reactive stroma formation is present in all the models developing invasive carcinomas. In addition, numerous models with multiple genetic alterations display aggressive phenotypes characterized by sarcomatoid carcinomas and metastases, which is presumably a histological manifestation of epithelial-mesenchymal transition. The significant progress in development of improved models of PCa has already accelerated our understanding the complex biology of PCa and promises to enhance development of new approaches to prevention, detection and treatment of this common malignancy.
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