Regional Response to ONC201 in Pediatric High-Grade Glioma

Pediatric high-grade glioma with H3K27M mutation (H3K27M-pHGG) carries a particularly poor prognosis and new targeted therapies are needed to address this disease. Case report data has shown that ONC20, a dopamine receptor (DRD2) antagonist, is effective against H3K27M-pHGGs. This means that ONC20 binds to the DRD2 receptor, thereby blocking the effects of any other molecules that would otherwise bind. Researchers have conducted an ongoing integrated clinical analysis of adult and pediatric patients treated in multiple early phase clinical trials to assess the regional response to treatment with ONC201 in H3K27M-pHGG. An exciting result of this ongoing analysis shows that patients with thalamic-H3K27M-HGG demonstrated an exceptional response to ONC201. The current estimates for progression free survival and overall survival are better than any previously seen. In this project, the goal will be to study the mechanism of regional response to ONC201 in pre-clinical models of H3K27M-pHGG. The Children’s Brain Tumor Network will provide researchers with pHGG cell lines that have annotated molecular and regional information. This integrative experimental approach will establish the mechanism behind the H3K27M-pHGG development and open new windows for therapies targeted to this hard to treat tumor.