Ewing sarcoma is a type of tumor that forms from a certain kind of cell in bone or soft tissue. It can occur at any age, but it is more likely to occur in children and teenagers. Ewing sarcoma treatment usually begins with chemotherapy; surgery to remove the cancer usually follows. Other treatments, including radiation therapy, might be used in certain situations. Now, Cold Spring Harbor Laboratory (CSHL) researchers have discovered a new drug target for Ewing sarcoma. Their experiments suggest Ewing sarcoma could potentially be stopped by developing a drug that blocks the protein known as ETV6.

Their study is published in Nature Cell Biology in an article titled, “ETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation.”

CSHL professor Christopher Vakoc, MD, PhD, who led the research on ETV6 said: “This protein is present in all cells. But when you perturb the protein, most normal cells don’t care. The process by which the sarcoma forms turns this ETV6 molecule—this relatively innocuous, harmless protein that isn’t doing very much—into something that’s now controlling a life-death decision of the tumor cell.”

When postdoctoral researcher Yuan Gao, PhD, blocked ETV6 in Ewing sarcoma cells grown in the lab, she observed a significant transformation. “The sarcoma cell reverts back into being a normal cell again,” she said. “The shape of the cell changes. The behavior of the cells changes. A lot of the cells will arrest their growth. It’s really an explosive effect.”

The researchers hope their findings may pave the way for potential therapies for Ewing sarcoma that work by switching off ETV6. They believe their biochemical analyses could help guide drug development.

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