Grant: Team Grant: Terry Fox New Frontiers Program in Cancer

Prostate cancer is the most commonly diagnosed non-skin cancer in men and a leading cause of cancer-death. Progression to castration resistance following hormonal therapy is the main obstacle to improving survival and is the central focus of our Terry Fox New Frontiers Program on Prostate Cancer Progression. Our hypothesis is that the development of hormone/castration resistance can be defined in terms of specific gene and cellular changes, some of which may serve as treatment targets or biomarkers to predict disease outcomes. Our objectives are to: i) identify genomic, molecular and cellular mechanisms responsible for castrate resistance, ii) use this information to develop new therapies to delay disease progression, and iii) accelerate bench-to bedside translation of our discovery science. Our multidisciplinary team of 20 scientists and clinicians has demonstrated synergy and benefits of working as a team towards these common objectives. Since our renewal in 2006, we have published >115 papers, obtained >100 patents, out-licensed 6 novel therapeutics, and completed 8 phase I/II trials of novel agents discovered as a direct consequence of laboratory research performed under the auspices of our Terry Fox Program. Leading in this regard is OGX-011, which has shown a 7-month survival gain. This direct translation to the clinic is the payoff that we strive for. This application consists of 8 highly integrated projects grouped into 4 areas: Target Discovery, Cell Biology Mechanisms, Molecular & Cellular Targets, and Clinical Evaluation. All projects are supported by 5 major cores: Advanced Genomics & Bioinformatics, Pathology & Molecular Imaging, Animal Models, Analytical Pharmacology, and Translational Trials. In summary, our Terry Fox Program is an ideal example of how team science accelerates discovery of underlying mechanisms of prostate cancer progression, leads to development of new therapies, and translates laboratory research into clinical practice.