Ridding cells of EYA3 boosts chemotherapy response in Ewing sarcoma

Scientists have identified a protein that makes some children and teenagers afflicted with Ewing sarcoma more resistant than others to chemotherapy.

The genetic mutation that gives rise to this childhood bone cancer also leads to high levels of the protein in question, EYA3. This suggests that EYA3 levels could help clinicians determine a more accurate prognosis for a person with Ewing sarcoma, and could guide decisions regarding how aggressively to treat the disease.

Lowering EYA3 levels also could increase the effectiveness of current therapies for Ewing sarcoma. After the recent discovery that EYA3 is a DNA repair molecule, Heide L. Ford, PhD, of the University of Colorado Cancer Center in Aurora, and colleagues showed that the protein behaved similarly in Ewing sarcoma, helping cancerous tissue survive during chemotherapy and recover afterward. Most important, when the protein was knocked down in the cancer cells, those cells became sensitized to chemotherapy, and were less able to repair DNA damage than were control cells.

“Our next step is to test small molecule inhibitors against EYA3 to determine which inhibitors best sensitize Ewing sarcomas to chemotherapy,” commented Ford. Her remarks appeared in a statement issued by the University of Colorado, Denver, to announce her team's findings, which were published by the journal Molecular Cancer Research.

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