Forefront News from the front lines at Rutgers Cancer Institute of New Jersey Fishing for Answers Three large laboratories a single agent or combined with other therapies for more effective prostate cancer treatment. Our studies provide the best possible treatment strategy for using these novel Bmi-1 inhibitors in human clinical trials,” notes Rutgers cancer institute researcher Hatem Sabaawy, MD, PhD, who is also an assistant professor of medicine at Rutgers Robert Wood Johnson medical School. Rutgers cancer institute Deputy Director and Associate Director for Basic Science Eileen White, PhD, notes the collaboration across multiple disciplines “paints a true picture of translational science.” I The work, supported by grants from the Department of Defense (W81XWH-12-1-0249), National Cancer Institute (P30 CA072720), Rutgers Cancer Institute, Wellcome Trust (#092687) and New Jersey Health Foundation, appeared in the June 2016 edition of ‘Clinical Cancer Research’ (DOI: 10.1158/10780432.CCR-15-3107). and a set of tiny fish at Rutgers Cancer Institute of New Jersey are shining new light on a treatment alternative for those with prostate cancer whose disease is resistant to therapy. Treatment resistance is common in ad- Kudos! vanced prostate cancer due to remaining stem cells called tumor-initiating cells (Tics) that defy anti-cancer therM. Mehnert, MD apy. With funding from the Department of Defense Prostate cancer Research Program and other support, the laboratories of Hatem Sabaawy, Joseph Bertino and Isaac Kim identified a novel therapy for prostate cancer. The team focused on finding a drug that would specifically affect the “onoff switch” of a protein known as Bmi1. This protein is essential for cellular self-renewal and survival of Tics. investigators identified drug compounds that block Bmi-1, using tissue samples from prostate cancer patients. This was done through laboratory cell culture and animal models, including zebrafish, which were used as a novel, rapid and inexpensive drug screen. The zebrafish were used as living incubators to house human prostate cancer cells from each patient to allow for the testing of different doses and combinations of Bmi-1-blocking drugs. This screening mechanism also indicated how toxic the compounds were and allowed the team to focus on safer drugs. Once an effective drug and regimen were identified, the work was confirmed using mouse models. “The antitumor activities of this Bmi1 blocking drug were independent of hormonal or prior treatment conditions; therefore, it could be utilized as Janice (below), director of the Phase i/investigational Therapeutics Program at Rutgers cancer institute of New Jersey and associate professor of medicine at Rutgers Robert Wood Johnson medical School, is a co-principal investigator on a $2,271,427 grant (R01cA 19397001A1) awarded by the National cancer institute. She is collaborating with Ryan J. Sullivan, MD (left, bottom), at massachusetts General Hospital cancer center in examining the safety and efficacy of the investigational drug navitoclax when combined with other therapies in the treatment of BRAFmutant melanoma and other BRAFmutant solid tumors. When compared to chemotherapy, anti-cancer therapies designed to block the BRAF and mek pathways that are known for promoting tumor growth improve response rate, progression free survival and overall survival in more than 50 percent of patients with BRAF-mutant melanoma that has spread to other parts of the body. While these drugs have become standards of care, patients still experience disease progression and die of their disease. Drs. mehnert and Sullivan and colleagues aim to improve the effectiveness of BRAF-directed therapy by targeting the death of cancer cells. I STeVe HOckSTei N De b b i e Vog e l 4 I Cancer Connection I Autumn 2016