Novobiocin to target DNA-repair weakness in BRCA-mutated cancers
Novobiocin-mediated polymerase theta inhibition in homologous recombination repair-deficient cancers
This project uses the antibiotic novobiocin to block a DNA-repair enzyme and help kill BRCA-mutated cancers, including tumors that have become resistant to PARP drugs.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Dana-Farber Cancer Inst NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11192750 on NIH RePORTER |
What this research studies
From a patient perspective, researchers will use tumor cells in the lab and patient-derived tumor grafts in mice to see whether novobiocin alone or combined with the PARP blocker talazoparib can better kill BRCA-mutated breast, ovarian, and pancreatic cancers. They will compare the combination against each drug by itself and include tumors that are sensitive to PARP inhibitors as well as tumors that acquired resistance. The team will measure molecular signs of DNA damage (g-H2AX, pRPA, RAD51 foci), micronuclei formation, and activation of immune signaling (cGAS/STING) to understand how the drugs work. The goal is to identify whether this approach could move toward clinical testing for patients with homologous recombination repair defects.
Who could benefit from this research
Good fit: Ideal candidates are people with advanced BRCA1/2-mutated breast, ovarian, or pancreatic cancers, especially if their tumors are resistant to PARP inhibitors.
Not a fit: Patients whose tumors do not have homologous recombination (BRCA) defects or who cannot tolerate antibiotic or PARP therapies are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, this work could lead to a new treatment option for people with BRCA-mutated cancers, including those whose tumors no longer respond to PARP inhibitors.
How similar studies have performed: PARP inhibitors are an established treatment for BRCA-mutant cancers, while POLQ inhibition with novobiocin is a newer, promising approach shown to work in preclinical models but not yet proven in patients.
Where this research is happening
Boston, United States
- Dana-Farber Cancer Inst — Boston, United States (Active)
Researchers
- Principal investigator: Shapiro, Geoffrey I. — Dana-Farber Cancer Inst
- Study coordinator: Shapiro, Geoffrey I.
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.