Targeting harmful EZH2 activity in aggressive leukemia
Dissecting and targeting canonical and non-canonical oncogenic functions of EZH2 in caner
['FUNDING_R01'] · DUKE UNIVERSITY · NIH-11258526
This project develops a new drug-like molecule that removes the EZH2 protein to try to stop aggressive MLL1-rearranged leukemia.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | DUKE UNIVERSITY (nih funded) |
| Locations | 1 site (DURHAM, UNITED STATES) |
| Trial ID | NIH-11258526 on ClinicalTrials.gov |
What this research studies
MLL1-rearranged leukemias are aggressive blood cancers with poor outcomes, and researchers are looking for better treatments. The team found that EZH2 not only represses genes but also helps activate cancer-driving genes by binding partners like c-MYC. They are using PROTAC technology to create degraders (including a lead compound called MS177) that pull EZH2 and its cancer-promoting partners apart and remove them from cells. In lab studies MS177 breaks down both the usual EZH2 complexes and the non-standard interactions and works better than enzyme-blocking drugs, with the goal of moving toward treatments for patients.
Who could benefit from this research
Good fit: Patients whose leukemia carries an MLL1 (MLL1-rearranged/MLL fusion-positive) abnormality would be the most likely candidates for related clinical trials.
Not a fit: Patients without MLL1 rearrangements or whose disease is driven by other pathways are less likely to benefit from this EZH2-targeting approach.
Why it matters
Potential benefit: If successful, this approach could lead to more effective therapies for people with MLL1-rearranged leukemia.
How similar studies have performed: Traditional drugs that block EZH2's enzyme activity have shown limited benefit, while PROTAC degraders like MS177 are a newer strategy with promising preclinical results but no proven patient benefit yet.
Where this research is happening
DURHAM, UNITED STATES
- DUKE UNIVERSITY — DURHAM, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: WANG, G GREG — DUKE UNIVERSITY
- Study coordinator: WANG, G GREG
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.