Targeting a DNA repair weakness in Ewing sarcoma
Official title: Exploiting a Novel DNA Repair Defect in Ewing Sarcoma
Funded at Dana-Farber Cancer Inst · NIH-11240282 · Data updated 2026-11-12
This project aims to exploit a DNA repair weakness to develop new treatments for children and young adults with Ewing sarcoma.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Dana-Farber Cancer Inst NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | December 4, 2024 |
| Project end | November 30, 2029 |
| Funding year | 2026 |
| Award (this year) | $523,292 |
| NIH project number | 5R01CA296618-02 |
| Project ID | NIH-11240282 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates would be children, adolescents, and young adults diagnosed with Ewing sarcoma, particularly those with relapsed or metastatic disease or whose tumors show the specific DNA repair defect.
✕Less likely to help
Patients without Ewing sarcoma or whose tumors lack the specific DNA repair defect are unlikely to benefit from these targeted approaches.
What this research studies
Researchers found that Ewing sarcoma cells have a specific fault in a DNA repair pathway called microhomology-mediated end joining (MMEJ) caused by changes in the EWSR1 gene and loss of POLQ protein. The team uses laboratory models, CRISPR gene editing, and cancer cell lines to study how that repair fault makes tumors unusually sensitive to certain chemotherapy drugs and radiation. By understanding this weakness, they plan to test drug combinations in preclinical experiments that could selectively kill Ewing sarcoma cells. The work aims to translate those findings into treatment strategies that could be offered at clinical centers.
Why it matters
Potential benefit: If successful, this work could lead to targeted therapies that make chemotherapy or radiation more effective for patients with Ewing sarcoma, especially those with relapsed or metastatic disease.
How similar studies have gone: Approaches that target DNA repair defects (for example, PARP inhibitors in BRCA-mutant cancers) have worked in other tumors, but exploiting MMEJ/POLQ defects in Ewing sarcoma is a newer and less-tested idea.
Where this research is happening
-
Dana-Farber Cancer Inst
Boston, United States Active
Researchers
- Principal investigator: D'andrea, Alan D. — Dana-Farber Cancer Inst
- Study coordinator: D'andrea, Alan D.
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RAPID: A patient-centered, fast-tracked drug trial platform for young people with relapsed Ewing sarcoma and DSRCT
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A scientist at Case Western Reserve University is studying a specific protein, ETV6, that helps a rare bone cancer called Ewing sarcoma, with the goal of finding targeted therapies that could spare healthy cells.
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A funded project at Stanford aims to use immune markers on Ewing Sarcoma to develop targeted immunotherapies that work in children and adults with this cancer.
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Ewing sarcoma: how DNA repair weaknesses affect risk and treatment
A clinician-researcher team at Dana-Farber is studying how DNA damage repair weaknesses help drive Ewing sarcoma in kids and teens, with the goal of better predicting risk and guiding therapy.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.