Identifying a molecular-based treatment for a viral skin cancer - Drywall Cart - Mast Climbers Manu

"This research effort shows the speed at which genomics canidentify 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. NationalCancer Act, researchers have strived to discover the underlyingproblems 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 wasresponsible for tumor development in most cases of the disease.

Atleast four out of five healthy adults world-wide are infected withMCV, which usually doesn't cause any symptoms. "The virus remains in the skin cells, and in most cases, no damageis 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 inthe U.S. are caused by MCV infection." In quick succession, the team devised tests to identifyvirus-induced MCC, and began unraveling the biochemical pathwaysthat encourage tumor formation. In their latest project, they"knocked out" a key viral protein called T antigen and found thatMCV directly elevates a cellular protein called survivin. Survivin prevents cells from dying and supports cell division, theresearchers said. They found that a drug called YM155, which turnsoff the survivin gene again, was an extremely potent killer of MCCcells in test tubes and was able to suppress the growth of humantumors that had been established in experimental mice.

Incomparison, 1,360 other drugs - including most of the commonchemotherapy drugs - were screened and failed to both kill MCCcells and prevent tumor growth at levels commonly achieved inpatients. One of these drugs was able to kill tumor cells inculture dishes, but made no impact on the MCC tumors in mice. Itremains a promising candidate drug since it may have betteractivity in people and is readily available. A multicenter clinical trial of YM155, a still-experimentalanti-cancer drug that is made by Deerfield, Ill.-based Astellas, isexpected to begin in the next six months to determine itseffectiveness in MCC patients.

The trial will be led locally byPitt School of Medicine assistant professor Hussein Tawbi, M.D.,Ph.D., and professor John Kirkwood, M.D., who also is co-leader ofthe UPCI Melanoma Program, through the Eastern Cooperative OncologyGroup, a multicenter cooperative group supported by the NationalCancer Institute (NCI), part of the National Institutes of Health. Typically, neither the cause of a cancer nor the target for acancer drug is initially known, so most treatments have developedover decades through trial-and-error. Most therapies affect bothhealthy tissues and cancer cells, resulting in side effects thatlimit the drug dose that can safely be given. This study, incontrast, was a "rational" drug study where the underlying cellulardefect caused by the virus was first discovered through geneticstudies and then a drug targeting this process was tested.

Survivinis needed during fetal development, but not in healthy adult cells,and YM155 was not toxic to the mice. "Scientists can now quickly come up with answers to complexproblems, like cancer, using human genetics," Dr. Moore noted. "Inless than five years, we have gone from knowing very little aboutMCC to knowing its exact cause and are devising new, preciselytargeted and less-toxic therapies." Additional References Citations.

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