New treatments for glioblastoma with mismatch repair defects
Vulnerabilities of MMR-deficient glioblastoma
Researchers are trying drug combinations and signaling blockers to help adults whose glioblastoma tumors have mismatch repair defects and resist standard chemotherapy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Virginia NIH-funded |
| Lab location | 1 site (Charlottesville, United States) |
| Project ID | NIH-11144296 on NIH RePORTER |
What this research studies
This project focuses on glioblastoma tumors that have mismatch repair (MMR) defects, which make them hypermutated and hard to treat. Scientists will test combinations of calcium channel blockers (carboxyamidotriazole, mibefradil, verapamil) and agents targeting TGF-β in tumor cell lines and laboratory models that mimic these MMR-deficient tumors. They will compare responses in MMR-deficient models versus non-defective models to find treatments that work preferentially against the resistant tumors. Promising findings would be used to guide future clinical testing for adults with these specific tumor defects.
Who could benefit from this research
Good fit: Ideal candidates are adults with recurrent or treatment-resistant glioblastoma whose tumors show mismatch repair defects such as mutations in MSH6 or MSH2.
Not a fit: Patients whose glioblastoma does not have mismatch repair defects, and most pediatric cases, may not receive direct benefit from these specific findings.
Why it matters
Potential benefit: If successful, this work could reveal drug combinations that overcome resistance in MMR-deficient, hypermutated glioblastoma and point toward new treatment options for affected patients.
How similar studies have performed: A few pediatric case reports showed immunotherapy responses and early lab studies hint that calcium channel blockers may help, but adult clinical success has been limited so this combined-therapy approach remains exploratory.
Where this research is happening
Charlottesville, United States
- University of Virginia — Charlottesville, United States (Active)
Researchers
- Principal investigator: Purow, Benjamin W. — University of Virginia
- Study coordinator: Purow, Benjamin W.
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.