Combination treatment effective against melanoma

The Cancer Institute of New JerseyApr 3 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.