Functionally defined therapeutic targets in diffuse intrinsic pontine glioma

被引：386

作者：

Grasso, Catherine S. ^{[1
,2
]}

Tang, Yujie ^{[2
,3
,4
,5
]}

Truffaux, Nathalene ^{[6
]}

Berlow, Noah E. ^{[7
]}

Liu, Lining ^{[2
,3
,4
,5
]}

Debily, Marie-Anne ^{[8
]}

Quist, Michael J. ^{[1
]}

Davis, Lara E. ^{[8
]}

Huang, Elaine C. ^{[9
]}

Woo, Pamelyn J. ^{[2
,3
,4
,5
]}

Ponnuswami, Anitha ^{[2
,3
,4
,5
]}

Chen, Spenser ^{[2
,3
,4
,5
]}

Johung, Tessa B. ^{[2
,3
,4
,5
]}

Sun, Wenchao ^{[2
]}

Kogiso, Mari ^{[10
]}

Dui, Yuchen ^{[10
]}

Qi, Lin ^{[10
]}

Huang, Yulun

Huett-Cabezas, Marianne ^{[11
,12
]}

Warrenm, Katherine E. ^{[12
]}

Le Dret, Ludivine ^{[6
]}

Meltzerm, Paul S. ^{[13
]}

Mao, Hua ^{[10
]}

Quezado, Martha ^{[12
]}

van Vuurden, Dannis G. ^{[14
,15
]}

Abraham, Jinu ^{[9
]}

Fouladi, Maryam ^{[16
]}

Svalina, Matthew N. ^{[17
]}

Wang, Nicholas ^{[1
]}

Hawkins, Cynthia ^{[18
,19
]}

Nazarian, Javad ^{[20
]}

Alonso, Marta M. ^{[21
]}

Raabe, Eric H. ^{[11
,12
]}

Hulleman, Esther ^{[14
,15
]}

Spellman, Paul T. ^{[1
]}

Li, Xiao-Nan ^{[10
]}

Keller, Charles ^{[9
,17
]}

Pal, Ranadip ^{[7
]}

Grill, Jacques ^{[6
,22
,23
]}

Monje, Michelle ^{[2
,3
,4
,5
]}

机构：

[1] Oregon Hlth & Sci Univ, Ctr Spatial Syst Biomed, Dept Mol & Med Genet, Portland, OR 97201 USA

[2] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA

[6] Univ Paris Sud, CNRS, Gustave Roussy, UMR 8203, Villejuif, France

[7] Texas Tech Univ, Elect & Comp Engn, Lubbock, TX 79409 USA

[8] Univ Evry Val dEssone, Dept Biol, Evry, France

[9] Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, Pediat Canc Biol Program, Portland, OR 97201 USA

[10] Baylor Coll Med, Texas Childrens Canc Ctr, Mol Neurooncol Lab, Houston, TX 77030 USA

[11] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA

[12] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA

[13] NCI, Bethesda, MD 20892 USA

[14] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol & Hematol, Amsterdam, Netherlands

[15] Vrije Univ Amsterdam, Med Ctr, Neuroncol Res Grp Canc Ctr Amsterdam, Amsterdam, Netherlands

[16] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA

[17] Childrens Canc Therapy Dev Inst, Ft Collins, CO USA

[18] Univ Toronto, Dept Pediat Lab Med, Toronto, ON, Canada

[19] Univ Toronto, Hosp Sick Children, Labatt Brain Tumor Res Ctr, Toronto, ON M5G 1X8, Canada

[20] Childrens Natl Hlth Syst, Ctr Res Inst, Washington, DC USA

[21] Univ Hosp Navarra, Dept Oncol, Pamplona, Spain

[22] Univ Paris Sud, Inst Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France

[23] Parke Davis Res Unit, Inst Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France

来源：

NATURE MEDICINE | 2015年 / 21卷 / 06期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

HISTONE H3.3; MUTATIONS; INHIBITION; SUBGROUPS; CELL;

D O I：

10.1038/nm.3855

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：555 / 559

页数：5

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