Public release date: 9-May-2012 [ | E-mail | Share ]

Contact: Anita Srikameswaran SrikamAV@upmc.edu 412-578-9193 University of Pittsburgh Schools of the Health Sciences

PITTSBURGH, May 9 Four years after they discovered the viral roots of a rare skin cancer, researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine have now identified a molecule activated by this virus that, in animal studies, could be targeted to selectively kill the tumor cells. The treatment will soon be tested in patients.

Merkel cell carcinoma (MCC), a skin cancer that is more common among seniors and those with weakened immune systems, could not be readily diagnosed at one time, and it still has a very poor prognosis, said Patrick S. Moore, M.D., M.P.H., and Yuan Chang, M.D., both of the Cancer Virology Program at UPCI and senior authors of a study that appears online today in Science Translational Medicine.

"This research effort shows the speed at which genomics can identify molecular causes for cancer and then point the way toward a rational and targeted treatment," Dr. Moore noted. "Since the inception of the 1971 U.S. National Cancer Act, researchers have strived to discover the underlying problems that trigger tumor development."

In 2008, the team first described the new Merkel cell polyomavirus (MCV) in Merkel cell carcinoma. Within a year, they showed it was responsible for tumor development in most cases of the disease. At least four out of five healthy adults world-wide are infected with MCV, which usually doesn't cause any symptoms.

"The virus remains in the skin cells, and in most cases, no damage is done," Dr. Chang said. "But when mutations occur to this virus, it can cause cancer. Most of the 1,500 new MCC cases per year in the U.S. are caused by MCV infection."

In quick succession, the team devised tests to identify virus-induced MCC, and began unraveling the biochemical pathways that encourage tumor formation. In their latest project, they "knocked out" a key viral protein called T antigen and found that MCV directly elevates a cellular protein called survivin.

Survivin prevents cells from dying and supports cell division, the researchers said. They found that a drug called YM155, which turns off the survivin gene again, was an extremely potent killer of MCC cells in test tubes and was able to suppress the growth of human tumors that had been established in experimental mice. In comparison, 1,360 other drugsincluding most of the common chemotherapy drugswere screened and failed to both kill MCC cells and prevent tumor growth at levels commonly achieved in patients. One of these drugs was able to kill tumor cells in culture dishes, but made no impact on the MCC tumors in mice. It remains a promising candidate drug since it may have better activity in people and is readily available.

A multicenter clinical trial of YM155, a still-experimental anti-cancer drug that is made by Deerfield, Ill.-based Astellas, is expected to begin in the next six months to determine its effectiveness in MCC patients. The trial will be led locally by Pitt School of Medicine assistant professor Hussein Tawbi, M.D., Ph.D., and professor John Kirkwood, M.D., who also is co-leader of the UPCI Melanoma Program, through the Eastern Cooperative Oncology Group, a multicenter cooperative group supported by the National Cancer Institute (NCI), part of the National Institutes of Health.

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Pitt team uses genomics to identify a molecular-based treatment for a viral skin cancer