Discovery of a new drug rich in possible ways to treat Ewing sarcoma, a frequently deadly cancer of children and the younger generation, and also the previously unknown mechanism behind it, come hand-in-surrender a new study by researchers from Huntsman Cancer Institute (HCI) on the University of Utah. The report appears in the current online issue of the journal Oncogene.
“Ewing sarcoma is almost always caused by a cancer-causing protein called EWS/FLI,” said Stephen Lessnick, M.D., Ph.D., director of HCI’s Center for Children’s Cancer Research, professor in the Department of Pediatrics at the University of Utah School of Medicine, and an HCI investigator.
“Ewing sarcoma is actually always the effect of a cancer-causing protein called EWS/FLI,” said Stephen Lessnick, M.D., Ph.D., director of HCI’s Center for Children’s Cancer Research, professor inside the Department of Pediatrics for the University of Utah School of Medicine, and an HCI investigator.
Inside lab, Lessnick and his awesome colleagues found make fish an enzyme, called lysine specific demethylase (LSD-1), interacts with EWS/FLI to show off gene expression in Ewing sarcoma. By turning off specific genes, the EWS/FLI-LSD1 complex causes Ewing sarcoma development.
“For a long time, we’ve known that EWS/FLI works by binding to DNA and turning on genes that activate cancer formation,” said Lessnick. “It was a surprise to find out that it turns genes off as well.
“The beauty, if there’s anything beautiful about a nasty disease like this, is that if we can inhibit EWS/FLI, we can inhibit this cancer, because EWS/FLI is the master regulator of Ewing sarcoma,” Lessnick added.
While Lessnick and his colleagues worked on EWS/FLI in their basic research laboratory, Sunil Sharma, M.D., director of HCI’s Center for Investigational Therapeutics, professor within the Department of drugs at the University of Utah, and an HCI investigator, had already devoted to LSD-1 just as one target for brand spanking new cancer treatments coupled with been earning a living for a very extensive period to design drugs that might inhibit its actions.
“We had found that LSD-1 was important for regulation of a variety of properties in several different cancers, including acute leukemias, breast and prostate cancers,” Sharma said.
“After Steve showed that LSD-1 was directly regulating the function of EWS/FLI, we teamed up with him to see whether the LSD inhibitors we had discovered worked in Ewing sarcoma models,” Sharma said. “Our tests in Ewing sarcoma tissue cultures show they are extremely potent.”
Lessnick and Sharma are actually working together to further test LSD inhibitors in animal models when they work toward approval of a first-in-man medical trial. In addition, Lessnick’s basic science research on LSD-one out of Ewing sarcoma continues.
“This is a great example of how collaboration between the therapeutics and basic science programs can lead to new treatments for patients—one of HCI’s highest goals,” said Sharma.
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