Projects

Specialized Programs of Research Excellence (SPORE) … promoting interdisciplinary research and moving basic research findings from the laboratory to clinical settings…

 

The PNW Prostate Cancer SPORE consists of four institutions that have large, multi-disciplinary teams of investigators and laboratories dedicated to prostate cancer research and a history of working closely together within this larger milieu. The respective teams of clinicians and researchers at these institutions bring considerable scientific depth and breadth required for confronting the most challenging problems blocking progress in our ultimate goal of reducing the morbidity and mortality associated with prostate cancer. This SPORE provides the blueprint for building a large coordinated translational prostate cancer effort spanning the Pacific Northwest.

In addition to Fred Hutchinson Cancer Research Center, participating centers include the University of Washington; the University of British Columbia and its affiliate, the Prostate Centre of Vancouver General Hospital; and Oregon Health & Science University. The integrated, bench-to-bedside approach of the PNW Prostate SPORE involves basic, clinical and population sciences research teams that are devoted to exploring a fundamental understanding of cancer biology, including molecular genetics and genomics.

The consortium aims to focus on finding molecular and other factors associated with the risk of prostate cancer recurrence and progression as well as its response – and resistance – to treatment. To this end, it is structured around five research projects, some ongoing and some new.

Project 1: Molecular Predictors of Prostate Cancer Progression and Mortality

Co-Leaders: Janet Stanford, Ph.D., Daniel Lin, M.D.

Prostate cancer (PCa) is a major cause of mortality, but it is not currently possible to accurately predict which tumors will remain indolent vs become life-threatening. To identify prognostic biomarkers, the proposed study will utilize samples and data from a population-based cohort of 1,458 PCa patients to assess genome-wide DNA methylation…

Project 2: Targeting LSD1 in Prostate Cancer

Co-Leaders: Joshi Alumkal, M.D., Tomasz Beer, M.D.

This proposal will apply novel insights regarding the role of LSD1 in promoting ligand and AR-independent CRPC survival and lethal progression. Using in vitro cell lines, in vivo xenograft models, and tumor biopsies from men with CRPC enrolled in a phase 1 study of a novel LSD1 inhibitor, we will establish the specific mechanisms by which LSD1 acts…

Project 3: Targeting SEMA3C in Castration Resistant Prostate Cancer

Co-Leaders: Martin Gleave, M.D., Christopher Ong, Ph.D.

We postulate that under selective pressures of castration and AR pathway inhibitor treatment, stress-activated networks increase SEMA3C activity to activate key RTK (c-Met, EGFR/ERBB2) and downstream (src, AKT, MAPK) pathways, including cross-talk and activation of the AR. Since these are important drivers of resistance to AR pathway inhibition, targeting SEMA3C has a strong biologic rationale…

Project 4: Clinical Development of Therapeutic Strategies Targeting Damage Responses in the Prostate Tumor Microenvironment

Co-Leaders: Peter Nelson, M.D., Bruce Montgomery, M.D.

Metastatic prostate carcinoma is a disease with high lethality, attributable in part to the rapid development of resistance to anti-neoplastic drugs. The successful completion of our studies may alter current concepts of treatment resistance, both to genotoxic and to pathway directed therapeutics…


Project 5: Exploiting Mechanisms of Response and Resistance to Next Generation Androgen Pathway Antagonists

Co-Leaders: Elahe Mostaghel, M.D., Ph.D., Stephen Plymate, M.D.

The efficacy of agents targeting the androgen receptor (AR) axis in men with castration-resistant prostate cancer (CRPC) may differ markedly based on tumor-specific differences in the induction of AR pathway components. A critical need is to define how the presence or development of these markers predicts for response to sequential or combination therapies…