Targeting integrated metabolic and epigenetic pathways in lethal childhood ependymomas. Targeting integrated metabolic and epigenetic pathways in lethal childhood ependymomas

Childhood Posterior Fossa-A ependymomas (PFAs) have limited treatment options. Integrated metabolic/epigenetic analyses performed to discover therapeutic targets in PFAs demonstrated enhanced glycolysis and TCA-cycle metabolism. PFAs exhibit low H3K27me3, as in H3K27M gliomas. Therefore, we subjected them to panobinostat which kills H3K27M cells, along with the metabolic inhibitor metformin. Combined treatment increased H3K27me3, suppressed metabolism and demonstrated potent therapeutic efficacy in vitro and in vivo, suggesting promising therapeutic strategies. Overall design: H3K27ac ChIP sequencing was performed on 3 posterior fossa (PF) and 3 supratentorial (ST) ependymoma samples