ALDH's role in resistance to PARP-blocking drugs for BRCA/HR-deficient ovarian cancer
Role of ALDH in PARP inhibitor resistance in HR-deficient ovarian cancer
This work looks at whether higher levels of the enzyme ALDH make PARP-blocking drugs less effective for people with BRCA-mutant or homologous recombination–deficient ovarian cancer.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Ohio State University NIH-funded |
| Lab location | 1 site (Columbus, UNITED STATES) |
| Project ID | NIH-11330579 on NIH RePORTER |
What this research studies
PARP inhibitors can work well for ovarian cancers with BRCA1/2 or other homologous recombination (HR) defects, but many patients eventually develop resistance. The team found that PARP inhibitors can raise activity of the enzyme ALDH, especially the ALDH1A1 form, and that ALDH1A1 seems to boost a backup DNA-repair route (MMEJ) by increasing Pol θ, which may help cancer cells survive treatment. Researchers will use tumor cells and laboratory models to define how ALDH1A1 and Pol θ drive resistance after PARP inhibitor exposure and will test whether blocking ALDH1A1 can make tumors sensitive to PARP drugs again. The goal is to link the molecular findings to possible ways to keep PARP therapies working longer for patients.
Who could benefit from this research
Good fit: People with ovarian cancer that is BRCA1/2-mutated or otherwise homologous recombination–deficient, especially those who have received or are receiving PARP inhibitor therapy, would be most relevant.
Not a fit: Patients whose tumors are not HR-deficient or whose drug resistance arises from unrelated mechanisms may not benefit from findings focused on ALDH1A1-driven resistance.
Why it matters
Potential benefit: If confirmed, this could point to new ways to prevent or reverse PARP inhibitor resistance so these drugs remain effective longer for people with BRCA-mutant or HR-deficient ovarian cancer.
How similar studies have performed: PARP inhibitors are an established effective option for BRCA-mutant ovarian cancer and prior work links ALDH to general chemoresistance, but the specific ALDH1A1–Pol θ mechanism for PARP inhibitor resistance is a newer and relatively untested idea.
Where this research is happening
Columbus, UNITED STATES
- Ohio State University — Columbus, United States (Active)
Researchers
- Principal investigator: Wang, Qien — Ohio State University
- Study coordinator: Wang, Qien
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.