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Functionally defined therapeutic targets in diffuse intrinsic pontine glioma

by Quist, Michael J , Hütt-Cabezas, Marianne , Qi, Lin , Raabe, Eric H , Spellman, Paul T , Liu, Lining , Fouladi, Maryam , Le Dret, Ludivine , Wang, Nicholas , Huang, Elaine C , Johung, Tessa B , Mao, Hua , Sun, Wenchao , Berlow, Noah E , Davis, Lara E , Grill, Jacques , Hawkins, Cynthia , Quezado, Martha , Debily, Marie-Anne , Woo, Pamelyn J , Svalina, Matthew N , Nazarian, Javad , Pal, Ranadip , Ponnuswami, Anitha , Kogiso, Mari , Du, Yuchen , Abraham, Jinu , Warren, Katherine E , Truffaux, Nathalene , Monje, Michelle , Grasso, Catherine S , Huang, Yulun , van Vuurden, Dannis G , Alonso, Marta M , Chen, Spenser , Meltzer, Paul S , Keller, Charles , Tang, Yujie , Hulleman, Esther , Li, Xiao-Nan

in 13/106 / 13/31 / 38/22 / 38/23 / 38/39 / 38/91 / 59 / 59/5 / 631/67/1922 / 64/60 / Animals / Benzazepines - administration & dosage / Biomedicine / Brain Stem Neoplasms - drug therapy / Brain Stem Neoplasms - genetics / Brain Stem Neoplasms - pathology / brief-communication / Cancer / Cancer Research / Cancer therapies / Care and treatment / Children & youth / Disease Models, Animal / Drug Synergism / Gene mutations / Genetic aspects / Glioma - drug therapy / Glioma - genetics / Glioma - pathology / Gliomas / Humans / Hydroxamic Acids - administration & dosage / Indoles - administration & dosage / Infectious Diseases / Metabolic Diseases / Molecular Medicine / Neurosciences / Physiological aspects / Pyrimidines - administration & dosage / Ribonucleic acid / RNA / Sequence Analysis, RNA / Synergistic effect / Xenograft Model Antitumor Assays

2015

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2015

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Journal Article

Functionally defined therapeutic targets in diffuse intrinsic pontine glioma

Quist, Michael J,

Hütt-Cabezas, Marianne,

Qi, Lin,

Raabe, Eric H,

Spellman, Paul T,

Liu, Lining,

Fouladi, Maryam,

Le Dret, Ludivine,

Wang, Nicholas,

Huang, Elaine C,

Johung, Tessa B,

Mao, Hua,

Sun, Wenchao,

Berlow, Noah E,

Davis, Lara E,

Grill, Jacques,

Hawkins, Cynthia,

Quezado, Martha,

Debily, Marie-Anne,

Woo, Pamelyn J,

Svalina, Matthew N,

Nazarian, Javad,

Pal, Ranadip,

Ponnuswami, Anitha,

Kogiso, Mari,

Du, Yuchen,

Abraham, Jinu,

Warren, Katherine E,

Truffaux, Nathalene,

Monje, Michelle,

Grasso, Catherine S,

Huang, Yulun,

van Vuurden, Dannis G,

Alonso, Marta M,

Chen, Spenser,

Meltzer, Paul S,

Keller, Charles,

Tang, Yujie,

Hulleman, Esther,

Li, Xiao-Nan

2015

Overview

The study describes the use of integrative approaches to search for candidate therapeutic targets for DIPG, and the identification of an HDAC inhibitor as a potential treatment strategy 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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Publisher

Nature Publishing Group US,Nature Publishing Group

Subject

13/106

/ 13/31

/ 38/22

/ 38/23

/ 38/39

/ 38/91

/ 59