The continued hypothesis of this application is that a Specialized Program of Research Excellence (SPORE) in Prostate Cancer at the University of Michigan will reduce the morbidity and mortality of prostate cancer. The SPORE supports an interactive group of basic and clinical investigators in a translational research program directed at developing new interventions in the diagnosis, prevention, and treatment of prostate cancer. This competing renewal application consists of six multidisciplinary research projects: Osteoclastogenesis as a Target for Prostate Cancer Osseous Metastases Therapy: The 5-year translational goal of this project is to test in a randomized phase II trial whether the addition of the bisphosphonate zoledronate to chemotherapy will have added therapeutic benefit for patients with hormone refractory prostate cancer. The Role of Protease Activated Receptor-1 (PAR1) in Prostate Cancer Metastasis: The 5-year translational goal of this project is to identify agents that will inhibit PAR1 to treat metastatic prostate cancer utilizing circulating prostate cancer cells as a surrogate marker for therapeutic response. Signature Lethal Biomarkers of Prostate Cancer: The 5-year translational goal of this project is the identification of biomarkers associated with lethal prostate cancer. Defining Genetic Risk Factors for Brothers of Men with Prostate Cancer: The 5-year translational goal of this project is to identify genes that are associated with the risk of prostate cancer in men with one or more brothers affected with prostate cancer. A secondary goal is to characterize genes that are predictive of clinically aggressive prostate cancer in men with a family history of the disease. The Role of Activated in Prostate Cancer (AIPC) Gene in Prostate Cancer Development: The 5-year translational goal of this project is to identify the non-androgen dependent growth mechanism of prostate cancer utilizing hormonally treated radical prostatectomy specimens. Multiple Mechanisms of Androgen Resistance in Prostate Cancer Progression: The 5-year translational goal of this project is to identify other members of the androgen receptor promoter complex that may serve as targets for the development of better therapies for hormone naive prostate cancer. These projects are complemented by ongoing successful career development and development research programs. The projects and programs are supported by a strong ongoing Institutional commitment of money and space as well as four cores: Administration, Biostatistics, Tissue and Clinical Applications. This SPORE program continues to place premiums on rigorous scientific reviewing of it's translational research programs, pairing of basic and clinical investigators, drawing on the expertise of scientists outside the field of prostate cancer, and utilizing flexibility to fund promising new research approaches. The interaction of our multidisciplinary group of investigators clearly makes the Prostate SPORE program at the UMCCC greater than the sum of its individual parts.