Blocking p300 to prevent PARP drug resistance in acidic tumors
Targeting p300 to Overcome PARP inhibitor resistance induced by acidic tumor microenvironment
This project looks at whether blocking a protein called p300 can help PARP drugs work better for people with BRCA-mutant ovarian cancer when tumors become acidic.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Tx Md Anderson Can Ctr NIH-funded |
| Lab location | 1 site (Houston, United States) |
| Project ID | NIH-11159411 on NIH RePORTER |
What this research studies
Researchers are studying why low pH (acidic) tumor environments make PARP drugs like olaparib less effective in epithelial ovarian cancer, especially in patients with BRCA1/2-related repair defects. In the lab they use cell models, animal studies, and CRISPR genetic screens that identified the epigenetic regulator p300 as a key driver of acidity-induced resistance. The team will test drugs that block p300 together with PARP inhibitors to see if the combination restores cancer cell killing and PARP trapping. They will also analyze tumor samples for biomarkers that could predict who would benefit and help guide future clinical testing.
Who could benefit from this research
Good fit: Ideal candidates are people with epithelial ovarian cancer, particularly those with BRCA1/2 mutations or homologous recombination deficiency who have shown or risk developing resistance to PARP inhibitors.
Not a fit: Patients without ovarian cancer, without BRCA/HDR-related defects, or whose treatment fails for reasons unrelated to tumor acidity or p300 activity are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, this approach could restore or extend the effectiveness of PARP inhibitors for patients whose BRCA-related ovarian cancers have become resistant due to an acidic tumor microenvironment.
How similar studies have performed: Combining PARP inhibitors with drugs that target epigenetic regulators has shown promise in preclinical and some early clinical work, but targeting p300 specifically to counteract acidity-driven resistance is a newer, mainly preclinical approach.
Where this research is happening
Houston, United States
- University of Tx Md Anderson Can Ctr — Houston, United States (Active)
Researchers
- Principal investigator: Zhang, Rugang — University of Tx Md Anderson Can Ctr
- Study coordinator: Zhang, Rugang
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.