New Compounds Offer Hope for Treatment of Ewing Sarcoma

Two compounds were found to suppress the activity of a transcription factors molecule, showing promise in the treatment of Ewing sarcoma.

The new compounds derive from mithramycin, a drug previously investigated for the treatment of Ewing sarcoma.

EWS-FLI1 is a key factor in gene regulation, but in patients with Ewing sarcoma, EWS-FLI1 incorrectly switches certain genes on and off, leading to uncontrolled cellular proliferation and eventual tumors.

The combination of chemotherapy, radiation, and surgery isn’t very effective in patients with metastatic cancer or who have relapsed because EWS-FLI1 is difficult to target.

“EWS-FLI1 is unique to Ewing sarcoma and is present in the majority of cases, which offers an excellent opportunity for developing precise therapies that combat cancer cells with less chance of affecting normal, healthy cells,” said senior author Patrick Grohar, MD, PhD. “At the same time, these findings lay the groundwork for devising ways to target transcription factors in other cancers, which historically has been challenging.”

These 2 compounds have high potential for additional studies because of their ability to suppress EWS-FLI1 activity more effectively than mithramycin with far less toxic effects.

“Although we are hopeful our findings will lead to new, more effective therapies for Ewing sarcoma, we also believe they serve as a precedent for targeting transcription factors in other tumor types,” Grohar said. “We're excited to complete the preclinical work, which will help us prioritize one of the compounds for translation into a clinical trial.”