How the APE2 DNA-repair protein helps breast cancers that can't use homologous recombination
Deciphering the function of the APE2 nuclease during repair by alternative end-joining and its role in HR-deficient cells
This project looks at whether disrupting the APE2 protein can make breast cancers that can't repair DNA properly—including tumors that resist PARP inhibitors—more likely to die.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Colorado NIH-funded |
| Lab location | 1 site (Boulder, UNITED STATES) |
| Project ID | NIH-11239802 on NIH RePORTER |
What this research studies
Researchers use genome-wide CRISPR screens and biochemical assays to map how APE2 supports an alternative DNA repair route called alternative end-joining (Alt-EJ). They perform reporter-based repair tests and telomere-fusion experiments in HR-deficient cancer cell lines and models to see how dependent these cells are on APE2. The team will define APE2’s enzymatic role in Alt-EJ and test whether its loss or inhibition sensitizes tumors that lack homologous recombination. Results are intended to highlight potential drug targets and biomarkers that could guide future therapies for PARP-resistant cancers.
Who could benefit from this research
Good fit: People with HR-deficient breast cancer—such as those with BRCA1/2-related tumors—or patients whose tumors have become resistant to PARP inhibitors would be the most relevant group.
Not a fit: Patients whose tumors are homologous recombination–proficient or who have cancers unrelated to HR defects are unlikely to benefit directly from this specific research.
Why it matters
Potential benefit: If successful, this work could identify new drug targets to kill HR-deficient breast cancers, including tumors that no longer respond to PARP inhibitors.
How similar studies have performed: PARP inhibitors are an established therapy for HR-deficient cancers, but targeting Alt-EJ or APE2 is a newer strategy supported mainly by early preclinical data rather than clinical success to date.
Where this research is happening
Boulder, UNITED STATES
- University of Colorado — Boulder, United States (Active)
Researchers
- Principal investigator: Arnoult, Nausica C. — University of Colorado
- Study coordinator: Arnoult, Nausica C.
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.