Cancer chemicals that weaken tumor DNA repair
Oncometabolites, DNA Repair, and Cancer
This research looks at whether chemicals made by some tumors stop cancer cells from fixing DNA, especially in cancers with IDH1/2, FH, or SDH mutations such as certain leukemias, brain, kidney, and adrenal tumors.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Yale University NIH-funded |
| Lab location | 1 site (New Haven, United States) |
| Project ID | NIH-11248773 on NIH RePORTER |
What this research studies
I have a tumor-driving mutation like IDH1/2, FH, or SDH; the researchers found that the chemicals produced by these mutant tumors — 2-hydroxyglutarate, succinate, and fumarate — can interfere with the cell's ability to repair DNA breaks. In laboratory experiments and analyses of tumor material they showed these metabolites compete with alpha-ketoglutarate to inhibit the histone demethylase KDM4B, leading to chromatin changes that mask signals needed for homology-directed DNA repair. The work used molecular studies, cell models, and human tumor samples and has been published in major journals. Learning how these metabolites cause DNA repair defects could point to new treatment strategies that target that weakness.
Who could benefit from this research
Good fit: People with cancers known to carry IDH1/2, FH, or SDH mutations — for example some acute myeloid leukemias, gliomas, cholangiocarcinomas, renal cell carcinomas, and paragangliomas/pheochromocytomas — would be most relevant to this research.
Not a fit: Patients whose tumors do not produce high levels of 2HG, succinate, or fumarate, or who lack the relevant metabolic mutations, are unlikely to benefit directly from this research.
Why it matters
Potential benefit: If successful, this work could enable treatments that exploit DNA repair defects in tumors with elevated oncometabolites, potentially making therapies more effective for those patients.
How similar studies have performed: Previous studies showed that IDH-mutant tumors produce 2HG and clinical work targets IDH mutations, while the specific link between oncometabolites and impaired homologous DNA repair is a newer discovery with experimental support.
Where this research is happening
New Haven, United States
- Yale University — New Haven, United States (Active)
Researchers
- Principal investigator: Glazer, Peter M — Yale University
- Study coordinator: Glazer, Peter M
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.