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Donor to School of Medicine research says melanoma is a personal issue

Medicine@Yale, 2017 - Apr May

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Jon Sokoloff lost his mother to melanoma 15 years ago. Since then, he and his wife Sheryl have sought to do everything they can to support research into more effective treatments. The couple began funding research through the Melanoma Research Alliance (MRA) 10 years ago. In that time, they have seen stunning improvements in the outlook for people with this type of cancer.

“Eighteen years ago, when my mother got this diagnosis, it was total despair. There was nothing you could do,” says Sokoloff. “It has been rewarding to watch the dramatic improvement in the availability of therapies that can combat the disease.”

Sokoloff has seen firsthand how well these new therapies can work. His cousin, whose advanced melanoma metastasized to his brain and lungs, is now cancer free after participating in a clinical trial with the immunotherapy drug ipilimumab (Yervoy®).

“We are just at the beginning of the wonderful drugs out there to be developed,” Sokoloff says.

The Sokoloffs and MRA have made a new three-year, $900,000 award to a School of Medicine research team so it can further investigate the microenvironment in which melanoma tumors live. The team includes Marcus W. Bosenberg, M.D., Ph.D., associate professor of dermatology and of pathology, Susan M. Kaech, Ph.D., Waldemar Von Zedtwitz Professor of Immunobiology; Richard G. Kibbey, M.D., Ph.D., associate professor of medicine (endocrinology) and of cellular and molecular physiology; and Sidi Chen, Ph.D., assistant professor of genetics and systems biology. The team has the broad range of expertise needed to undertake the goals of the research, including the discovery of factors related to tumor growth that render T cells in the immune system too weak to fight the tumors.

“We believe our idea presents an entirely different perspective on how immunosuppression may be generated within tumors,” Bosenberg says.

In an earlier study also funded by the Sokoloffs and MRA, published March 2016 in Cell Reports, Bosenberg and colleagues identified an enzyme that plays a crucial role in melanoma growth. They reported that DNMT3B—a DNA methyltransferase enzyme—regulates melanoma formation. When the investigators reduced the enzyme in mice, melanoma development was delayed due to the enzyme’s effect on the protein Rictor, which controls tumor growth. Inhibitors of DNMT3B are currently being developed as a future cancer therapy by a Yale team led by Bosenberg.

Sokoloff says he is optimistic that recent advances in melanoma research will also lead to progress elsewhere. “Several of the early immunotherapy drugs that were approved for melanoma are now being shown to have applications in other cancers, such as lung and brain cancer,” he says. “It is really the beginning of the immunotherapy tidal wave, which is one of the great hopes for combating cancer.”

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