For the first time, researchers have found a potential drug candidate that improved outcomes for patients with a type of childhood brain tumor for which there are no effective treatments.
Reviewed by Megan Craig, M.Sc.Aug 17 2023 The compound, called ONC201, nearly doubled survival for patients with diffuse midline glioma or diffuse intrinsic pontine glioma , compared to previous patients.
Diffuse midline gliomas including DIPG with a mutation called H3K27M are particularly aggressive, with an overall survival rate of 11-15 months. These tumors are most frequently found in children and young adults. The only available treatment is radiation, and even that is difficult as the tumors are located amid brain regions with critical functions.
ONC201 took an unusual path to a clinical trial. Initially designed to target dopamine receptors, which are upregulated in many different tumors, researchers saw that the drug passes the blood-brain barrier, one of the biggest challenges to designing drugs for brain tumors. Initial trials in glioblastoma were not successful, but a small number of patients with DMG that carried the H3K27M mutation had more promising results.
Related StoriesKoschmann called the finding "very much unexpected." The team found that increased L-2HG reversed tumor defining epigenetic signals causing tumor cells to differentiate more and divide less. The longer patients were on ONC201, the more tumors exhibited these epigenetic reversals.
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