Researchers show an oncolytic virus switches off cancer cell survival signal

Researchers from Boston University School of Medicine (BUSM) have identified a mechanism by which specific viruses acting as oncolytic agents can enter and kill cancer cells. This finding, which is currently featured in an online edition of the Journal of Virology, could help lead to the development of more targeted treatments against many types of cancer.

The study was conducted by Ewan F. Dunn, a postdoctoral fellow, under the direction of John H. Connor, an assistant professor of microbiology at BUSM.

The virus, known as vesicular stomatitis virus (VSV), is being developed in the Connor lab and in other international research laboratories to kill cancer cells. VSV is not a significant human pathogen.

VSV is sensitive to the innate immune response, which causes lymphocytes to release interferon and protect the body from developing an infection. Cancer cells lose the ability to respond in that way, said Dunn. “When cancer cells transform, they become non-responsive, leaving them vulnerable to viruses attacking the cell and its function.”

Previous research has shown that a major signaling pathway in cancer cells, called the AKT signaling pathway, is frequently turned on. AKT signaling is a cell survival signal, helping to keep the cancer cells alive. The team demonstrated was that VSV can switch off that signaling pathway, which suggests that a single viral protein could play a major role in cancer cell death.

“This study showed the important role of VSV in killing cancer cells through turning off a major survival signal,” added Connor. “The identification of this mechanism is fundamental to understanding how VSV and other oncolytic viruses function.”

This research study was funded by the National Institutes of Health.

Originally established in 1848 as the New England Female Medical College, and incorporated into Boston University in 1873, Boston University School of Medicine today is a leading academic medical center with an enrollment of more than 700 medical students and more than 800 masters and PhD students. Its 1,246 full and part-time faculty members generated more than $335 million in funding in the 2009-2010 academic year for research in amyloidosis, arthritis, cardiovascular disease, cancer, infectious disease, pulmonary disease and dermatology among others. The School is affiliated with Boston Medical Center, its principal teaching hospital, the Boston and Bedford Veterans Administration Medical Centers and 16 other regional hospitals as well as the Boston HealthNet.

www.bmc.org

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