Using DNA damage drugs to help the immune system fight uterine cancer
Official title: Targeting replication stress to engage DNA sensing STING pathway derived anti-tumor immunity to improve the therapeutic outcomes in uterine cancer
Funded at Dana-Farber Cancer Inst · NIH-11323901 · Data updated 2026-11-12
This project combines drugs that increase tumor DNA damage with immunotherapy to help people with recurrent microsatellite-stable uterine cancer who haven't responded to current treatments.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Dana-Farber Cancer Inst NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | May 1, 2024 |
| Project end | April 30, 2029 |
| Funding year | 2026 |
| Award (this year) | $511,431 |
| NIH project number | 5P01CA269021-03 |
| Project ID | NIH-11323901 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with recurrent or advanced microsatellite-stable (MMRP) uterine cancer who have not responded to or cannot tolerate pembrolizumab plus lenvatinib are the most likely candidates.
✕Less likely to help
Patients with mismatch repair–deficient (MSI‑high) uterine cancers or patients with other cancer types are unlikely to benefit from this specific approach.
What this research studies
This work focuses on microsatellite-stable (MSS) uterine cancers that often do not respond to existing immunotherapy. Researchers plan to use ATR or WEE1 inhibitors to raise DNA replication stress in tumor cells, which may activate the tumor's DNA-sensing STING pathway and make the cancer more visible to the immune system. They aim to pair these DNA damage–targeting drugs with immune checkpoint inhibitors to convert “cold” tumors into “hot” tumors that immune cells can attack. The program includes laboratory and translational studies and could lead to clinical testing at Dana‑Farber and collaborating sites.
Why it matters
Potential benefit: If successful, this approach could make immunotherapy effective for patients with recurrent MSS uterine cancer who currently have limited options.
How similar studies have gone: Early laboratory work and some early‑phase clinical studies suggest ATR/WEE1 inhibitors can boost tumor immune signaling, but combining them with immunotherapy in MSS uterine cancer is a relatively new approach.
Where this research is happening
-
Dana-Farber Cancer Inst
Boston, United States Active
Researchers
- Principal investigator: Zhao, Jean — Dana-Farber Cancer Inst
- Study coordinator: Zhao, Jean
Related research
Other NIH-funded projects on the same topics.
-
Modeling to Prevent and Control Uterine Cancer
A national modeling effort uses computer simulations to inform better prevention, screening, and treatment of uterine cancer for women.
-
Comparative modeling to guide uterine cancer care
This grant uses computer models to help doctors and patients understand how to make better decisions about uterine cancer care.
-
Dual ATR and PI3K-targeted therapy for uterine cancer
This project will try combining two drugs that block ATR and PI3K to better stop uterine cancers, especially tumors with ARID1A changes or other DNA replication stress.
-
WEE1-targeted treatment for uterine serous and p53-mutant uterine cancer
Testing a drug that blocks the WEE1 protein to try to shrink uterine serous cancers and other uterine cancers with p53 mutations.
-
Treating uterine (endometrial) cancer by targeting DNA damage and replication stress
This project develops new treatment approaches that exploit DNA repair weaknesses to help women with advanced or recurrent uterine (endometrial) cancer who need additional options.
-
Computer models to improve prevention and care for uterine (endometrial) cancer
Researchers are using computer models to compare prevention, screening, and treatment options for women at risk of or living with uterine cancer.
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.