Functionally defined therapeutic targets in diffuse intrinsic pontine glioma
Menée sur des lignées cellulaires de gliome infiltrant du tronc cérébral et à l'aide de xénogreffes, cette étude met en évidence l'activité antitumorale d'un traitement combinant le panobinostat, un inhibiteur d'histone désacétylase, et un composé appelé GSK-J4, un inhibiteur d'histone déméthylase
Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNA-seq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi–histone deacetylase inhibitor panobinostat demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat and the histone demethylase inhibitor GSK-J4 revealed that the two had synergistic effects. Together, these data suggest a promising therapeutic strategy for DIPG.