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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Benzazepines / administration & dosage*
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Brain Stem Neoplasms / drug therapy*
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Brain Stem Neoplasms / genetics
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Brain Stem Neoplasms / pathology
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Disease Models, Animal
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Drug Synergism
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Glioma / drug therapy*
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Glioma / genetics
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Glioma / pathology
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Humans
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Hydroxamic Acids / administration & dosage*
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Indoles / administration & dosage*
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Panobinostat
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Pyrimidines / administration & dosage*
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Sequence Analysis, RNA
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Xenograft Model Antitumor Assays
Substances
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Benzazepines
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GSK-J4
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Hydroxamic Acids
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Indoles
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Pyrimidines
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Panobinostat