PNP and SAMHD1 combination therapy for cancer
Targeting the PNP - SAMHD1 synthetic-lethal combination in cancer
Researchers are designing drugs that block SAMHD1 so, when combined with PNP-blocking medicines, people with T-cell cancers may respond better to treatment.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Albert Einstein College of Medicine NIH-funded |
| Lab location | 1 site (Bronx, United States) |
| Project ID | NIH-11321716 on NIH RePORTER |
What this research studies
The team uses precise chemistry and enzyme measurements to model how SAMHD1 works and to design molecules that tightly block it. They apply kinetic isotope effects and quantum chemistry to map the enzyme's transition state and create transition-state analog inhibitors. These new SAMHD1 inhibitors would be tested together with existing PNP-blocking drugs like Forodesine to trigger lethal buildup of DNA building blocks in T-cell cancer cells. The work is largely lab-based drug design and preclinical testing aimed at advancing promising compounds toward clinical trials.
Who could benefit from this research
Good fit: People with relapsed or refractory T-cell lymphomas or other T-cell cancers, especially tumors showing activity in the PNP/SAMHD1 pathway, would be the most likely candidates.
Not a fit: Patients whose tumors do not depend on the PNP/SAMHD1 pathway or people without cancer are unlikely to benefit from this research.
Why it matters
Potential benefit: If successful, this could make more T-cell and possibly other cancers respond to PNP-blocking therapy and improve cure rates.
How similar studies have performed: PNP inhibitors such as Forodesine have shown real clinical activity and cured a minority of peripheral T-cell lymphoma patients, but combining PNP blockade with SAMHD1 inhibition is a new and largely untested approach.
Where this research is happening
Bronx, United States
- Albert Einstein College of Medicine — Bronx, United States (Active)
Researchers
- Principal investigator: Schramm, Vern L. — Albert Einstein College of Medicine
- Study coordinator: Schramm, Vern L.
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.