Treating IDH-mutant cancers by activating the faulty enzyme
Targeting isocitrate dehydrogenase mutations by enzyme hyperactivation
This project tests a way to treat cancers with IDH mutations, like some leukemias and brain tumors, by activating the mutant enzyme to disrupt cancer growth.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Sloan-Kettering Inst Can Research NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11261162 on NIH RePORTER |
What this research studies
This project focuses on cancers that carry mutations in IDH enzymes, which make a molecule that helps cancer cells stay stuck in a stem-like state. Because many patients either do not respond to current IDH-blocking drugs or later become resistant, the team will try a different approach: pushing the mutant enzyme into an overactive state to undermine the cancer cell program. They will study specific resistance-linked mutations at the enzyme dimer interface and use lab models and patient-derived samples to test enzyme hyperactivation and candidate compounds. The work aims to find new ways to treat patients whose tumors no longer respond to existing IDH inhibitors.
Who could benefit from this research
Good fit: Ideal candidates are people whose tumors have confirmed IDH1 or IDH2 mutations, such as certain cases of AML, glioma, cholangiocarcinoma, or chondrosarcoma.
Not a fit: Patients without IDH mutations or whose cancers are driven by unrelated mechanisms are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, this could lead to new therapies for patients with IDH-mutant cancers who do not respond to or who develop resistance to current IDH inhibitors.
How similar studies have performed: IDH inhibitors have produced durable responses and FDA approvals in some cancers, but the concept of deliberately hyperactivating mutant IDH enzymes is novel and not yet tested in patients.
Where this research is happening
New York, United States
- Sloan-Kettering Inst Can Research — New York, United States (Active)
Researchers
- Principal investigator: Intlekofer, Andrew Michael — Sloan-Kettering Inst Can Research
- Study coordinator: Intlekofer, Andrew Michael
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.