Pediatric brain tumors have surpassed leukemia as the leading cause of cancer-related death in children. Several landmark studies from the last two decades have shown that many pediatric brain tumors are driven by epigenetic dysregulation within specific developmental contexts. One of the major determinants of epigenetic control is the histone code, which is orchestrated by a number of enzymes categorized as writers, erasers, and readers. Bromodomain and extra-terminal (BET) proteins are reader proteins that bind to acetylated lysines in histone tails and play a crucial role in regulating gene transcription. BET inhibitors have shown efficacy in a wide range of cancers, and a number have progressed to clinical phase testing. Here, we review the evidence for BET inhibitors in pediatric brain tumor experimental models, as well as their translational potential.
Keywords: BET inhibitor; atypical teratoid rhabdoid tumor; diffuse intrinsic pontine glioma; embryonal tumor with multilayer rosettes; ependymoma; epigenetics; medulloblastoma; pediatric brain tumors.