Blocking Wnt signaling in ovarian cancer that no longer responds to PARP drugs
Targeting Wnt signaling in therapy-resistant ovarian cancer
This work tests whether blocking a cell signal called Wnt can help immune therapies fight ovarian cancers that have stopped responding to PARP inhibitor drugs.
Quick facts
| Grant type | R37 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Colorado Denver NIH-funded |
| Lab location | 1 site (Aurora, UNITED STATES) |
| Project ID | NIH-11369043 on NIH RePORTER |
What this research studies
Researchers use tumor cells grown in the lab and patient-derived tumor grafts grown in mice to study why some high-grade serous ovarian cancers stop responding to PARP inhibitors. They are examining how Wnt/β-catenin signaling makes tumors hide from the immune system by raising PD-L1 and lowering IRF1 and by changing macrophages. The team will test a new allosteric β-catenin inhibitor (1525), alone and combined with immune checkpoint blockade, to see if it restores immune attack and shrinks resistant tumors. Results will guide whether this combination approach could move into early human trials.
Who could benefit from this research
Good fit: Patients with high-grade serous ovarian cancer whose tumors have become resistant to PARP inhibitors, including those with BRCA1/2-related disease, would be the most likely candidates for future trials based on these results.
Not a fit: Patients with ovarian cancers that remain PARP-sensitive, other tumor types, or those unable to receive immunotherapy may not benefit from this specific approach.
Why it matters
Potential benefit: If successful, this approach could restore treatment options for patients with PARP-resistant ovarian cancer by making tumors more responsive to immunotherapy and targeted drugs.
How similar studies have performed: Preclinical studies have shown Wnt/β‑catenin can drive immune exclusion and that blocking it can improve immunotherapy in models, but combining a first-in-class allosteric β‑catenin inhibitor with immunotherapy in PARP‑resistant ovarian cancer is a newer strategy.
Where this research is happening
Aurora, UNITED STATES
- University of Colorado Denver — Aurora, United States (Active)
Researchers
- Principal investigator: Bitler, Benjamin G — University of Colorado Denver
- Study coordinator: Bitler, Benjamin G
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.