Genetically modified mice and their use in developing therapeutic strategies for prostate cancer

Purpose: At the National Cancer Institute a comprehensive program has been developed for accelerating prostate cancer research, especially in the area of mouse models for human cancers. This review focuses on transgenic mouse models for elucidating the molecular and cellular processes that lead to prostate cancer initiation, progression and metastasis, and on their suitability for therapeutic and chemopreventive trials. Materials and Methods: Published data from MEDLINE, http://emice.nci.nih.gov/, our laboratory and other investigators are reviewed. Results: Currently no 1 mouse model displays the entire continuum of human prostate cancer initiation, development and metastasis. The loss or over expression of a single gene results primarily in epithelial hyperplasia, prostatic intraepithelial neoplasia or more aggressive localized adenocarcinoma. To date the only models that develop lung, liver and occasionally bone metastasis are those that express SV40 large T antigen. A number of models have been used to investigate the efficacy of androgen deprivation, lovastatin, vitamin D, the anti-inflammatory drug E-7869, genistein and (-)-epigallocatechin-3-gallate as therapeutic or chemopreventive agents. Noninvasive optical imaging technologies facilitate the detection of metastatic lesions and the effects of therapeutic agents on tumor regression. Conclusions: Integrating mouse studies with human clinical trials would ensure that mechanisms that promote prostate cancer are identified and potential therapeutic targets are validated.