Targeting POLQ to make cancer cells more vulnerable to treatment
Investigating DNA polymerase O in replication stress and cancer therapy
This project will see if blocking POLQ, a DNA repair protein, helps treatments that cause DNA replication stress kill cancer cells, especially in cancers like BRCA-deficient tumors.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Scripps Research Institute, the NIH-funded |
| Lab location | 1 site (La Jolla, United States) |
| Project ID | NIH-11173798 on NIH RePORTER |
What this research studies
Researchers will study how POLQ helps repair broken DNA when cancer cells experience replication stress and identify the specific repair steps that depend on POLQ. They will use laboratory cancer models (cells and preclinical models) to test whether inhibiting POLQ causes tumor cells to die under replication stress and whether combining POLQ inhibitors with ATR inhibitors increases that effect. The team will examine molecular markers of DNA damage, cell death, and genome instability to understand which tumors are most likely to respond. Findings will guide whether POLQ-targeting drugs or drug combinations could be developed for patients.
Who could benefit from this research
Good fit: Patients with tumors showing BRCA deficiency or other signs of high replication stress, or cancers that rely on alternative DNA repair pathways, would be the most likely candidates for POLQ-targeted approaches.
Not a fit: Patients whose cancers do not show replication stress or POLQ dependence, or those who cannot tolerate combination therapy, are less likely to benefit from POLQ-targeted strategies.
Why it matters
Potential benefit: If successful, this work could lead to new drugs or drug combinations that selectively kill cancers with high replication stress, expanding treatment options for patients with certain genetic tumor profiles.
How similar studies have performed: Preclinical studies have shown that POLQ inhibition can kill homologous-recombination-deficient cancer cells and can synergize with ATR inhibitors, but clinical testing of POLQ-targeted therapies remains limited.
Where this research is happening
La Jolla, United States
- Scripps Research Institute, the — La Jolla, United States (Active)
Researchers
- Principal investigator: Wu, Xiaohua — Scripps Research Institute, the
- Study coordinator: Wu, Xiaohua
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.