PROJECT SUMMARY/ABSTRACT The central theme of the Prostate Urothelial Cancer Program is to improve the treatment outcomes of prostate and urothelial cancers through translational research. While targeted therapies and resistance mechanisms as well as localized outcomes vary between these two cancers, we established this program based on the overlapping expertise and research personnel with the common interest in these two genitourinary malignancies. The long-term goal of the program is to reduce mortality for advanced prostate and urothelial cancers and improve outcomes for localized prostate and urothelial disease. After intensive investigation of the unmet medical needs in managing these two malignancies, we direct our research interests at three highly interactive research themes: First, to investigate mechanisms of drug resistance to current therapies; Second, to identify molecular targets and develop therapeutic approaches; and third, to improve outcomes for localized cancers. These three themes will be addressed through a translational approach of preclinical models and clinical applications across disciplines that lead to mechanism-based transformative treatments for prostate and urothelial cancers to overcome resistance, optimize response and minimize toxicity. Although they are different diseases, we are approaching the prostate and urothelial disease spaces in parallel, to have similar impact on reducing mortality for advanced prostate and urothelial cancer, while improving outcomes for localized prostate and urothelial disease. PROGRAM ASPECTS Co-leaders: Christopher Evans, MD; Allen Gao, MD, PhD; Chong-xian Pan, MD, PhD Members: 21 Total Grant Funding (ADC): $5.2 million Total Peer-Reviewed Funding (ADC): $4.8 million Total NCI funding (ADC): $1.8 million VA merit (additional funding not included above): $1,129,993 (7 projects funded) Total No. Publications: 360 Inter-programmatic publications: 186 (52%) Intra-programmatic publications: 103 (29%) Multi-institutional publications: 151 (42%) The Prostate Urothelial Cancer Program consists of 21 members from nine different departments and three different schools, with varied expertise in biochemistry, tumor biology, bioinformatics, urologic oncology, and medical oncology. The total peer-reviewed, cancer related funding (annual direct costs) has increased to $5.2 million (from $3.1 million in the previous period), with NCI funding increasing from $1.1 million in the previous period to $1.8 million in the current period.