Process of cancer cell self-digestion is target of new cancer therapies

27 May 2010

In an effort to improve current anticancer treatments, investigators at The Cancer Institute of New Jersey (CINJ) have been targeting a process known as autophagy, in which cancer cells eat themselves as a measure of self preservation under chemotherapy and radiation stress, thus prolonging tumour cell survival and inducing resistance to therapy. While preclinical studies have shown that inhibition of autophagy sensitises tumour cells to anticancer treatment, CINJ researchers have more recently had an opportunity to observe these effects in early-stage clinical trials involving autophagy inhibition by a drug commonly used to treat malaria. Their latest findings are being presented in abstract form next month in Chicago during the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO). CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.

At focus in these trials is the drug hydroxychloroquine - a common treatment for malaria and certain types of arthritis - which has been shown to block autophagy. Research from laboratories at CINJ indicates that drugs such as hydroxychloroquine may prevent cancer cells from becoming resistant to chemotherapy or to drugs that prevent the growth of cancer blood vessels. Through a number of Phase I and Phase II clinical trials at CINJ, investigators have been pairing hydroxychloroquine with other chemotherapy regimens in order to increase the effectiveness of treatment. Currently at focus are combination therapies for melanoma, as well as breast, lung, prostate, and colon cancers.

Along with determining the safety and efficacy of adding hydroxychloroquine to standard treatments, the team hopes that the results of these latest trials also will lead to the discovery of simple ways to detect autophagy in humans. For instance, the laboratory 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 tumours. In some of these trials, investigators are screening blood and tumour tissue for novel proteins such as p62, which could serve as an indicator to detect change in the autophagy process in humans.

"By further exploring mechanisms behind tumour cell survival, such as the process of autophagy, we will better understand how cancers evade standard treatments so that we can further develop new and more effective therapies," said Dr. Vassiliki Karantza, a medical oncologist at CINJ and assistant professor of medicine at UMDNJ-Robert Wood Johnson Medical School, who is the lead investigator.

The author team also includes Rebecca A. Moss, MD; Janice M. Mehnert, MD, Mark N. Stein, MD; Elizabeth Poplin, MD, Biren Saraiya, MD; Joseph Aisner, MD; Antoinette R. Tan, MD, Eileen White, PhD; and Robert S. DiPaola, MD, all of CINJ and UMDNJ-Robert Wood Johnson Medical School. Work in Dr. Karantza's laboratory is supported by the National Cancer Institute and the Damon Runyon Cancer Research Foundation.

The work represented by CINJ members is among the 5,000 abstracts being presented at the gathering, which is featuring more than 30,000 cancer specialists who will discuss the latest in cancer research, practice, policy and technology. The event is open to registered participants.

Source: The Cancer Institute of New Jersey