A new medication for a deadly cancer called Ewing sarcoma, a rare disease where cancer cells are present in bones of soft tissue and is mostly found in children and young adults, has been discovered by experts from Huntsman Cancer Insititute (HCI) at the University of Utah and published in the journal Oncogene.

Stephen Lessnick M.D., Ph.D., director of HCI’s Center for Children’s Cancer Research at the Department of Pediatrics at the University of Utah School of Medicine, and an HCI investigator said, “Ewing sarcoma is almost always caused by a cancer-causing protein called EWS/FLI.”

During the study, Lessnick and his team discovered that lysine specific demethylase (LSD-1), an enzyme, works with EWS/FLI to stop gene expression in Ewing Sarcoma. When certain genes are shut off, the EWS/FLI -LSD1 complex results in the development of Ewing sarcoma. Lessnick commented, “This makes LSD-1 an important target for the development of new drugs to treat Ewing sarcoma.”

Lessnick continued:

“For a long time, we’ve known that EWS/FLI works by binding to DNA and turning on genes that activate cancer formation. 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.”

Signs and symptoms of Ewing sarcoma include:

  • leukocytosis
  • anemia
  • sporadic fevers
  • increased sedimentation rate
  • localized pain
  • swelling
  • occasional bone pain

During the time, Lessnick and his team were working on EWS/FLI in the lab, Sunil Sharma, M.D., director of of HCI’s Center for Investigational Therapeutics, professor in the Department of Medicine at the University of Utah, and an HCI investigator, had already discovered that LSD-1 could potentially work as a target for new cancer drugs and had been researching for year to try to develop drugs to stop the cancer.

Sharma said:

“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. 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. Our tests in Ewing sarcoma tissue cultures show they are extremely potent.”

Now, Lessnick and Sharma are teaming up to continue testing LSD inhibitors on animals, and eventually they hope to test their findings on humans.

“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,” said Lessnick.

“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,” Sharma concluded.

Written by Christine Kearney