ONC201 is well suited to address this potential vulnerability as a selective DRD2 antagonist that exhibits blood-brain-barrier penetrance24 and p53-independent anti-cancer efficacy.14 Interestingly, DRD2 expression within the central nervous system is highest in midline structures of the brain (https://www.proteinatlas.org/ENSG00000149295-DRD2/brain),25 where the H3 K27M mutation is present and bystander effects of ONC201 have been documented in preclinical models.14 The role of ClpP, an additional direct target of ONC201, in DMGs is an area of active investigation.26 This evidence concerns the gene TP53 and cancer.