Blocking DNA polymerase theta in BRCA1-mutated cancers

Assessing DNA polymerase theta as a therapeutic target in BRCA1 mutant cancer

NIH-funded research Research Inst of Fox Chase Can Ctr · NIH-11296905

This project is developing drugs that block DNA polymerase theta to try to kill tumors with BRCA1 mutations while sparing normal cells.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionResearch Inst of Fox Chase Can Ctr NIH-funded
Lab location1 site (Philadelphia, United States)
Project IDNIH-11296905 on NIH RePORTER

What this research studies

You should know that this work focuses on cancers driven by BRCA1 gene mutations and is mostly done in the lab using cancer cells and models. Researchers will study how a DNA repair enzyme called polymerase theta helps some BRCA1-mutant tumors survive and why some do not depend on it. The team will test genetic changes and drug-like inhibitors to see which tumors are vulnerable and look for markers that predict who might benefit. These findings could guide future patient trials of polymerase theta inhibitors.

Who could benefit from this research

Good fit: People whose tumors carry BRCA1 mutations (for example certain breast or ovarian cancers) or patients with cancers that have become resistant to PARP inhibitors would be the most relevant future candidates.

Not a fit: Patients without BRCA1 mutations or tumors that use other DNA repair pathways are unlikely to benefit from polymerase theta–targeted therapies.

Why it matters

Potential benefit: If successful, this could lead to a new targeted treatment option for cancers with BRCA1 mutations, including cases resistant to current therapies.

How similar studies have performed: Laboratory genetic studies have shown that disabling Polθ can kill BRCA1-deficient cells and small-molecule Polθ inhibitors are in early development, but clinical benefit has not yet been proven.

Where this research is happening

Philadelphia, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.