ATR-targeted treatment for TP53-mutated myelodysplastic syndromes and acute myeloid leukemia
Project 4: Targeting ATR in TP53-mutated MDS/AML
This work combines an ATR-blocking drug with the chemotherapy drug decitabine to try to more effectively kill leukemia cells in people with TP53-mutated MDS or AML.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11195607 on NIH RePORTER |
What this research studies
Researchers found that leukemias with TP53 mutations often resist standard chemotherapy but respond to the drug decitabine. In lab experiments, decitabine caused DNA replication stress and activated ATR, and blocking ATR caused TP53-deficient leukemia cells to die. The team used DNA fiber assays, immunoblotting, and cell line models to show strong synergy between decitabine and ATR inhibitors. The goal is to develop this combination into a treatment approach and move toward testing in patients.
Who could benefit from this research
Good fit: People with confirmed TP53-mutated myelodysplastic syndromes or acute myeloid leukemia, especially those who have relapsed or not responded to standard therapies, would be the ideal candidates.
Not a fit: Patients without TP53 mutations or with other types of cancer are unlikely to benefit from this specific ATR-plus-decitabine approach.
Why it matters
Potential benefit: If successful, this approach could produce deeper remissions and longer survival for patients with TP53-mutated MDS or AML.
How similar studies have performed: Preclinical studies have shown synergy between decitabine and ATR inhibitors in TP53-deficient models, but clinical proof of benefit in patients is still limited.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Link, Daniel C — Washington University
- Study coordinator: Link, Daniel 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.