Using DNA damage drugs to help the immune system fight uterine cancer
Targeting replication stress to engage DNA sensing STING pathway derived anti-tumor immunity to improve the therapeutic outcomes in uterine cancer
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 ID | NIH-11323901 on NIH RePORTER |
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.
Who could benefit from this research
Good fit: 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.
Not a fit: Patients with mismatch repair–deficient (MSI‑high) uterine cancers or patients with other cancer types are unlikely to benefit from this specific approach.
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 performed: 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
Boston, United States
- Dana-Farber Cancer Inst — Boston, United States (Active)
Researchers
- Principal investigator: Zhao, Jean — Dana-Farber Cancer Inst
- Study coordinator: Zhao, Jean
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 below.