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Two heads are better than one, they say—and researchers from Huntsman Cancer Institute (HCI) at the University of Utah have proved it. By combining basic science research and clinical research, two HCI investigators reported in the journal Oncogene they had found a new drug that targets Ewing sarcoma cells. Ewing sarcoma is an often deadly bone cancer that primarily affects children and young adults. This type of cancer usually develops during puberty, when bones are growing quickly. It is most common in the long bones of the arms and legs, the pelvis, or the chest. It may also develop in flat bones of the skull or trunk.
“Ewing sarcoma is almost always caused by a protein called EWS/FLI,” explains Stephen Lessnick, MD, PhD, director of HCI’s Center for Children’s Cancer Research, professor in the Department of Pediatrics at the University of Utah, and an HCI investigator.
In the lab, Lessnick and his colleagues found that an enzyme called LSD1 works with EWS/FLI to turn off gene expression, which causes Ewing sarcoma to develop. “This makes LSD1 an important target for the development of new drugs to treat Ewing sarcoma,” Lessnick says.
Meanwhile, Sunil Sharma, MD, HCI’s senior director of Clinical Research and director of the Center for Investigational Therapeutics, and professor in the Department of Medicine at the University of Utah, had been working for several years to design drugs that would stop LSD1 from working.
“We teamed up with Dr. Lessnick to see whether the LSD inhibitor drugs we had discovered worked in Ewing sarcoma,” Sharma says. “Our tests in Ewing sarcoma tissue cultures show the drugs are extremely potent.”
Lessnick and Sharma are now working together to further test LSD inhibitors in animals. Their goal is to get approval for a first-in-man clinical trial.
Lessnick’s basic science research on LSD1 in Ewing sarcoma also continues. “We think it may play a larger role in Ewing sarcoma than simply turning off a handful of genes, and we’re looking into that,” says Lessnick.
The new discovery, says Sharma, “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.”
Lessnick says without this teamwork, it might have taken years before the drug could benefit Ewing sarcoma patients. “That’s the best possible outcome of a collaboration—to bypass years and years of waiting and bring cutting-edge treatments to these young kids as quickly as possible.”