Treating cancers by targeting faulty DNA repair
Targeting DNA Repair for Cancer Therapy.
Researchers are developing treatments that exploit DNA-repair weaknesses in cancers that produce abnormal metabolites like 2HG, fumarate, or succinate.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Yale University NIH-funded |
| Lab location | 1 site (New Haven, United States) |
| Project ID | NIH-11261736 on NIH RePORTER |
What this research studies
This work studies how certain tumors overproduce metabolites (2HG, fumarate, succinate) that impair a key DNA-repair pathway and create a specific weakness. The team uses laboratory experiments, unbiased CRISPR genetic screens, and small-molecule drug screens to identify the chromatin and end-protection factors involved and to find drugs that exploit these defects. They are also probing how tumors become resistant to PARP inhibitors and testing strategies to overcome resistance. Prior findings from this group have already supported early clinical trials that apply these ideas to patients with relevant tumor mutations.
Who could benefit from this research
Good fit: People with cancers known to overproduce oncometabolites—such as tumors with IDH1/2, fumarate hydratase (FH), or succinate dehydrogenase (SDH) mutations—would be the most relevant candidates for these approaches or related trials.
Not a fit: Patients whose tumors lack these oncometabolite-driven DNA repair defects are unlikely to benefit from these specific strategies.
Why it matters
Potential benefit: If successful, this research could produce targeted therapies that improve outcomes for patients whose tumors carry IDH1/2, FH, or SDH mutations by exploiting DNA repair defects.
How similar studies have performed: Prior laboratory work from this group and several early clinical trials have shown promising responses to PARP inhibitors in tumors with these oncometabolite-related DNA repair defects.
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.