Coordinated Blocking of Cancer Cell Survival Pathway Enhances Cell Death in Melanoma

Research from The Cancer Institute of New Jersey Presented at Annual AACR Meeting

Newswise — New Brunswick, N.J., April 2, 2012 – Research from The Cancer Institute of New Jersey (CINJ) shows that a coordinated effort to block signaling pathways that promote cancer cell growth and survival enhances programmed cell death in melanoma. The work is being presented in abstract form at the Annual Meeting of the American Association for Cancer Research (AACR) being held in Chicago this week. CINJ is a Center of Excellence of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. At focus is the intracellular pathway known as P13K/Akt/mTOR, which is a critical survival pathway in numerous malignancies, including melanoma. Temsirolimus, an FDA approved drug for the treatment of kidney cancer, has been found to block this pathway, thus inhibiting tumor growth, but it does not induce cell death. While it blocks the mTOR component of the pathway, temsirolimus activates another tumor survival pathway, known as autophagy, which recycles cellular components for reuse. The research by lead investigator Xiaoqi Xie, PhD, for a joint project directed by CINJ Associate Director for Basic Science Eileen White, PhD, and CINJ medical oncologist Janice Mehnert, MD, examined whether blocking autophagy increases the effectiveness of temsirolimus in the treatment of melanoma.

The investigators found that the survival of melanoma cells is dependent on autophagy. Previous research by the laboratory of Eileen White showed that the FDA-approved anti-malaria drug hydroxychloroquine blocks autophagy-mediated survival in human renal cancer. In this current laboratory study, when hydroxychloroquine was added to melanoma cell lines together with temsirolimus, it caused cell death by preventing the elimination of faulty mitochondria. Mitochondria are considered a vital energy source for the cell. The combination treatment with the two drugs showed a much higher efficacy compared to either drug given alone. “By making a concerted effort to block multiple survival pathways, scientists may have a new model to explore in developing new treatments for melanoma,” noted Dr. Xie, who is conducting postdoctoral work at UMDNJ-Robert Wood Johnson Medical School. Dr. Xie was awarded a 2012 Women in Cancer Research Scholar Award from the AACR to support the presentation of this work at the AACR 2012 national meeting.

Dr. White is a professor of molecular biology and biochemistry at Rutgers, The State University of New Jersey, and an adjunct professor of surgery at UMDNJ-Robert Wood Johnson Medical School. Dr. Mehnert is an assistant professor of medicine at UMDNJ-Robert Wood Johnson Medical School.

About The Cancer Institute of New JerseyThe Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center dedicated to improving the detection, treatment and care of patients with cancer, and serving as an education resource for cancer prevention. CINJ’s physician-scientists engage in translational research, transforming their laboratory discoveries into clinical practice, quite literally bringing research to life. To make a tax-deductible gift to support CINJ, call 732-235-8614 or visit www.cinjfoundation.org. CINJ is a Center of Excellence of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. Follow us on Facebook at www.facebook.com/TheCINJ. The CINJ Network is comprised of hospitals throughout the state and provides the highest quality cancer care and rapid dissemination of important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. System Partner: Meridian Health (Jersey Shore University Medical Center, Ocean Medical Center, Riverview Medical Center, Southern Ocean Medical Center, and Bayshore Community Hospital). Major Clinical Research Affiliate Hospitals: Carol G. Simon Cancer Center at Morristown Medical Center, Carol G. Simon Cancer Center at Overlook Medical Center, and Cooper University Hospital. Affiliate Hospitals: CentraState Healthcare System, JFK Medical Center, Robert Wood Johnson University Hospital Hamilton (CINJ Hamilton), Somerset Medical Center, The University Hospital/UMDNJ-New Jersey Medical School*, and University Medical Center at Princeton. *Academic Affiliate ###