NEW YORK (GenomeWeb News) – The Fred Hutchinson Cancer Research Center has won an $11.3 million competitive renewal grant from the National Cancer Institute to continue funding for a prostate cancer research consortium that pursues a range of projects focused on genetic and molecular medicine.
The grant renews support of the Pacific Northwest Prostate Cancer SPORE (Specialized Programs of Research Excellence) program, which launched in 2002, Fred Hutch said today.
Along with the Hutch, the prostate cancer SPORE partners 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 portfolio of projects is designed to improve prostate cancer prognosis and treatment response through approaches that are focused at the level of the individual patient, individual tumor, and individual therapy," Principal Investigator Peter Nelson, a member of the Fred Hutchinson Human Biology Division, said in a statement.
The SPORE research projects are supported by an infrastructure of research cores, also funded by the SPORE program, which provide resources and expertise in a range of areas, including administration, biospecimen resources, biostatistics, and clinical trial design.
The members of the Pacific Northwest Prostate Cancer SPORE are involved in five core projects that focus on discovering molecular and other factors involved prostate cancer recurrence and progression, as well as patient response and resistance to treatment.
In one effort, the partners are working to discover the inherited genetic and tumor epigenetic variations associated with prostate cancer progression and mortality, with the aim of finding biomarkers of aggressive prostate cancer. The hope is that these markers will help physicians determine which patients have a higher probability of having aggressive prostate cancer at the time they are diagnosed.
So far, this project has identified a panel of 22 SNPs associated with prostate cancer mortality, including five that have been validated in an independent cohort to be associated with a 50 percent higher risk of death.
Another project is focused on testing the hypothesis that the lysine-specific demethylase 1 (LSD1) gene promotes survival of prostate cancer cells, and leads to progression to lethality. The partners want to understand how LSD1 promotes cancer proliferation and progression, with the hope of developing ways to disable it.
In another program, the SPORE members are seeking to define and target pathways that drive advanced prostate cancer. They are focused on the mechanisms involved in a gene called SEMA3C in promoting resistance to androgen-deprivation therapy, with the goal of developing and testing a new therapy that targets the SEMA3C pathway in a preclinical model. They hope to eventually move this treatment into a phase 1 human clinical trial.
The consortium members are pursuing another clinical research project that aims to conduct preclinical and clinical trials to test the hypothesis that inhibiting DNA damage in the tumor microenvironment will enhance the response to treatment.
"Where the tumor cell resides and who its neighbors are influence its response and resistance to therapy," Nelson said. "Our preliminary findings indicate that the tumor microenvironment can influence the success or failure of more precise therapies."
Another program is focused on exploiting the mechanisms involved in resistance to treatment, identifying biomarkers for treatment response, and developing treatment strategies for patients with advanced, castration-resistant prostate cancer who do not respond to androgen-blocking drugs.
The initial results from this project have shown that advanced prostate cancers that are resistant to androgen-deprivation therapy have high concentrations or intratumor androgens. This has led to the development of androgen-pathway inhibitors, such as abiraterone, and preclinical studies of these drugs have shown new mechanisms of treatment resistance that could lead to other new classes of drugs.