Blocking the FEN1 enzyme to target cancers with DNA repair defects
FEN1 Endonuclease as a Synthetic Lethal Target for Cancer Therapy
Researchers are developing treatments that block the FEN1 enzyme to kill cancers with DNA repair defects, such as BRCA1/2-linked breast and ovarian cancers.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Diego NIH-funded |
| Lab location | 1 site (La Jolla, United States) |
| Project ID | NIH-11137105 on NIH RePORTER |
What this research studies
This project uses genetic data and lab models to test whether inhibiting the FEN1 enzyme can selectively kill cancer cells that have problems repairing DNA, like those with BRCA1 or BRCA2 mutations. The team is translating findings from yeast genetics to human cancer genes, running experiments in human cancer cell lines and preclinical models, and searching for drug-like molecules that hit FEN1. They will also look for biomarkers that predict which tumors are most likely to respond so future treatments can be targeted. All work is being done in laboratory and preclinical settings at the University of California San Diego and collaborating labs.
Who could benefit from this research
Good fit: Patients with cancers that carry BRCA1/BRCA2 mutations or other homologous recombination repair defects would be the most likely candidates for therapies developed from this work.
Not a fit: Patients whose tumors have intact DNA repair pathways or cancers driven by unrelated mechanisms may not benefit from FEN1-targeted treatments.
Why it matters
Potential benefit: If successful, this could lead to new targeted drugs that specifically kill tumors with DNA repair defects while reducing harm to normal cells.
How similar studies have performed: The PARP inhibitor approach has already used synthetic lethality successfully in BRCA-mutant cancers, but directly targeting FEN1 is a newer strategy that remains mainly at the laboratory and preclinical stage.
Where this research is happening
La Jolla, United States
- University of California, San Diego — La Jolla, United States (Active)
Researchers
- Principal investigator: Kolodner, Richard D — University of California, San Diego
- Study coordinator: Kolodner, Richard D
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.