Overcoming resistance to ONC201 in H3K27M diffuse midline glioma
Targeting EGFR/FOXG1-mediated resistance to ONC201 in H3K27M-mutant diffuse midline glioma
This work aims to learn how ONC201 kills tumors and how to stop tumor resistance in children and young adults with H3K27M diffuse midline glioma.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Michigan at Ann Arbor NIH-funded |
| Lab location | 1 site (Ann Arbor, United States) |
| Project ID | NIH-11261041 on NIH RePORTER |
What this research studies
Researchers will compare genetic features of patient tumors, focusing on EGFR and the brain-development factor FOXG1, to see why some tumors resist ONC201. They will test drug combinations in lab-grown tumor cells and mouse models to try to restore ONC201 sensitivity. The team will use tumor sequencing and existing patient data to link laboratory findings to real patients and identify markers that predict response. If promising combinations are found, those could guide future clinical testing at treatment centers.
Who could benefit from this research
Good fit: Children and young adults whose tumors carry the H3K27M mutation (diffuse midline glioma) are the main candidates who could be affected by this work.
Not a fit: Patients without the H3K27M mutation or with other types of brain tumors are unlikely to benefit directly from these findings.
Why it matters
Potential benefit: If successful, this could identify who is likely to benefit from ONC201 and suggest combination treatments that overcome resistance, potentially improving outcomes for patients with H3K27M-DMG.
How similar studies have performed: Early clinical use and lab studies of ONC201 have shown responses in some H3K27M-DMG patients and in animal models, but strategies to overcome EGFR- or FOXG1-linked resistance remain novel.
Where this research is happening
Ann Arbor, United States
- University of Michigan at Ann Arbor — Ann Arbor, United States (Active)
Researchers
- Principal investigator: Koschmann, Carl J — University of Michigan at Ann Arbor
- Study coordinator: Koschmann, Carl J
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.