Genetically engineered mouse models of prostate cancer

Objectives: Mouse models of prostate cancer are used to test the contribution of individual genes to the transformation process, evaluate the collaboration between multiple genetic lesions observed in a single tumour, and perform preclinical intervention studies in prostate cancer research. Methods: Mouse models for human prostate cancer are generated through genetic engineering of the mouse germline, introducing lesions that reflect those observed in human prostate cancer specimens. The optimal mouse model accurately reflects the pathogenesis of the disease including the sporadic nature of the initiating insult, the identity of the genetic lesions accumulated throughout the transformation process, the hormone dependency of the malignant cells, the incidence and tissue specificity of metastatic lesions, and the responses to therapeutic intervention. Results: Although this ultimate goal has not yet been reached, the currently existing mouse models for prostate cancer have yielded important insights. These mostly relate to the contribution of individual genes and the mechanism of oncogene collaboration in the early stages of the disease. Modelling metastatic and hormone-refractory prostate cancer, however, remains a major challenge. Conclusions: Mouse models have made an invaluable contribution in identifying the genetic lesions involved in high-grade prostatic intra-epithelial neoplasia lesions and locally invasive prostate cancer. Most mouse models are less accurate in modelling the progression to metastatic disease. Moreover, most mouse models for prostate cancer do not facilitate analysis of hormone-refractory prostate cancer, although this would constitute the most valuable contribution to preclinical testing of novel therapeutic intervention strategies for the human disease. (c) 2008 European Association of Urology and European Board of Urology. Published by Elsevier B.V. All rights reserved.