Turning a tumor's toxic byproducts into a treatment for IDH‑mutant brain tumors
Leveraging reactive metabolite generation in brain tumors
This project looks at whether blocking a detox enzyme in IDH‑mutant gliomas and combining that with radiation makes toxic metabolites build up and kill tumor cells.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Francisco NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-11239124 on NIH RePORTER |
What this research studies
Researchers found that IDH‑mutant gliomas produce a chemical (D‑2HG) that lowers a key antioxidant (GSH), making tumors depend on an enzyme called GLO1 to remove a harmful byproduct called methylglyoxal (MGO). They will use patient tumor samples and patient‑derived mouse models to test a brain‑penetrant GLO1 blocker (BBG) alone and together with radiation to force MGO to accumulate. Prior lab work showed that BBG plus radiation caused high MGO levels, damaged tumor proteins and DNA, and shrank tumors in mice. The team aims to define how best to exploit this metabolic weakness and move toward treatments that could be offered to patients.
Who could benefit from this research
Good fit: Adults with gliomas that carry IDH1 or IDH2 mutations would be the patients most likely to benefit from therapies developed from this work.
Not a fit: Patients with gliomas that do not have IDH mutations or with other types of brain tumors are unlikely to benefit from this specific metabolic approach.
Why it matters
Potential benefit: If successful, this approach could lead to a new therapy that makes radiation more effective and causes IDH‑mutant gliomas to shrink or stop growing.
How similar studies have performed: Preclinical studies using patient‑derived tumor models in mice have already shown tumor regression with GLO1 inhibition plus radiation, but this approach has not yet been tested in human clinical trials.
Where this research is happening
San Francisco, United States
- University of California, San Francisco — San Francisco, United States (Active)
Researchers
- Principal investigator: Viswanath, Pavithra — University of California, San Francisco
- Study coordinator: Viswanath, Pavithra
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.