Combining DNA-repair blockers to tackle hard-to-treat ovarian and uterine cancers
Overcoming treatment-resistant gynecological cancers by combination of DNA damage response inhibitors
This project will try drug combinations that block cancer cells' DNA repair to help people with treatment-resistant ovarian and uterine cancers.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pennsylvania NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11192367 on NIH RePORTER |
What this research studies
The team is developing combinations of DNA damage response (DDR) inhibitors aimed at ovarian and endometrial tumors that no longer respond to standard treatments, focusing on tumors with changes such as CCNE1 amplification, BRCA1/2 mutations, or ARID1A loss. They will expand patient-derived tumor models (PDXs and organoids) to include rare gynecologic tumor types and use those models to test which drug pairs are most effective. Researchers will perform deep genomic and transcriptomic analyses on those models and on patient samples from an ongoing early-phase clinical trial to find molecular signatures that predict response. The work is designed to identify targeted drug combinations and biomarkers that could guide future patient-focused trials.
Who could benefit from this research
Good fit: Ideal candidates are people with recurrent or treatment-resistant ovarian or endometrial cancers, particularly those whose tumors have CCNE1 amplification, BRCA1/2 mutations, or ARID1A loss.
Not a fit: People with early-stage disease already controlled by standard therapy or tumors lacking the genetic features under study may not receive direct benefit from this project.
Why it matters
Potential benefit: If successful, this could lead to new drug combinations and genetic tests that help people with resistant gynecologic cancers get more effective, personalized treatments.
How similar studies have performed: Related approaches like PARP inhibitors for BRCA-mutated ovarian cancer have helped some patients, but combining DDR inhibitors for CCNE1-amplified or ARID1A-deficient tumors is a newer approach still being explored.
Where this research is happening
Philadelphia, United States
- University of Pennsylvania — Philadelphia, United States (Active)
Researchers
- Principal investigator: Xu, Haineng — University of Pennsylvania
- Study coordinator: Xu, Haineng
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.