ONC201, initially discovered as p53-independent inducer of TRAIL and a dopamine receptor D2 antagonist, gained a fast-track designation from FDA for the treatment of adult recurrent H3K27M mutant high-grade glioma, after it showed efficacy in an adult patient with H3.3 K27M glioblastoma in a Phase 2 trial [26]. Here, TP53 is linked to central nervous system cancer.