Functionally defined therapeutic targets in diffuse intrinsic pontine glioma.
Catherine S GrassoYujie TangNathalene TruffauxNoah E BerlowLining LiuMarie-Anne DebilyMichael J QuistLara E DavisElaine C HuangPamelyn J WooAnitha PonnuswamiSpenser ChenTessa B JohungWenchao SunMari KogisoYuchen DuLin QiYulun HuangMarianne Hütt-CabezasKatherine E WarrenLudivine Le DretPaul S MeltzerHua MaoMartha QuezadoDannis G van VuurdenJinu AbrahamMaryam FouladiMatthew N SvalinaNicholas WangCynthia HawkinsJavad NazarianMarta M AlonsoEric H RaabeEsther HullemanPaul T SpellmanXiao-Nan LiCharles KellerRanadip PalJacques GrillMichelle MonjePublished in: Nature medicine (2015)
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.