Functionally defined therapeutic targets in diffuse intrinsic pontine glioma.

Grasso, Catherine S; Tang, Yujie; Truffaux, Nathalene; Berlow, Noah E; Liu, Lining; Debily, Marie-Anne; Quist, Michael J; Davis, Lara E et al. · Nat Med · 2015

basic_science · Level V

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Abstract

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.

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