Building off recent laboratory discoveries relating to how cancer cells become resistant to therapies that attempt to starve cancer, scientists at The Cancer Institute of New Jersey (CINJ) are now applying that knowledge to a process in which cancer cells eat themselves to downsize and resist therapy. The ultimate goal of this effort is to improve upon current anticancer treatments. Investigators have just launched a new clinical trial which targets a new combination therapy for advanced solid tumors that do not respond to traditional therapy or for whom no standard therapy exists. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School and New Jersey's only National Cancer Institute-designated Comprehensive Cancer Center -- one of only 40 in the country.
This latest study will offer patients a new treatment combination of the drugs hydroxychloroquine and sunitinib. Hydroxychloroquine, which is commonly used to treat malaria and certain types of arthritis, has been shown to block autophagy, the process by which cells eat themselves and become resistant to therapies that starve tumor cells. Research from laboratories at CINJ indicates that drugs such as hydroxychloroquine may prevent cancer cells from becoming resistant to anticancer treatments. Sunitinib is a drug that can starve tumor cells by blocking the growth of new blood vessels. In this trial, investigators will explore the benefit of adding hydroxychloroquine to enhance the effect of sunitinib.
Janice Mehnert, MD, medical oncologist at CINJ and assistant professor of medicine at UMDNJ-Robert Wood Johnson Medical School, is the lead researcher on the study. "Individually, these drugs have shown certain properties of halting tumor growth. By combining them, we are hoping to block the autophagy survival process and thus may be able to improve the outcomes of cancer therapy," she said.
Dr. Mehnert also hopes that the results of the trial will lead to the discovery of simple ways to detect autophagy in humans. For instance, the lab of CINJ's Associate Director of Basic Science, Eileen White, PhD -- who also is an adjunct professor of surgery at UMDNJ-Robert Wood Johnson Medical School and a professor at Rutgers, The State University of New Jersey -- found that a protein called p62 eliminates damaged proteins inside cancer cells, packages the waste and prepares it for disposal during the process of autophagy and may perhaps signal the presence of autophagy in tumors. "Given the findings of Dr. White's laboratory, we plan to examine blood and tumor tissue for novel proteins, such as p62, that may allow us to detect changes in the autophagy process in humans," Mehnert added.
Adults with advanced cancer in a solid tumor that is not responding to standard treatment are eligible to take part in the trial, although other criteria must be met. Prior to being accepted into the study, participants would undergo a number of tests including blood work and a physical.
If accepted for participation in the trial, individuals would receive six-week cycles of treatment, receiving both sunitinib and hydroxychloroquine in pill form through the end of treatment. The dose of sunitinib will remain the same throughout the treatment period, but the amount of hydroxychloroquine will increase during pre-determined periods of the treatment cycle. Participants would need to keep a pill diary and continue to undergo routine blood work during certain periods of the study.
The Cancer Institute of New Jersey
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