Functionally defined therapeutic targets in diffuse intrinsic pontine glioma.
Functionally defined therapeutic targets in diffuse intrinsic pontine glioma.
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DOI：
10.1038/nm.3855
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发表时间：
2015-06
期刊：
影响因子：
82.9
通讯作者：
Monje M
中科院分区：
文献类型：
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作者：
Grasso CS;Tang Y;Truffaux N;Berlow NE;Liu L;Debily MA;Quist MJ;Davis LE;Huang EC;Woo PJ;Ponnuswami A;Chen S;Johung TB;Sun W;Kogiso M;Du Y;Qi L;Huang Y;Hütt-Cabezas M;Warren KE;Le Dret L;Meltzer PS;Mao H;Quezado M;van Vuurden DG;Abraham J;Fouladi M;Svalina MN;Wang N;Hawkins C;Nazarian J;Alonso MM;Raabe EH;Hulleman E;Spellman PT;Li XN;Keller C;Pal R;Grill J;Monje M
弥漫性桥脑胶质瘤(DIPG)是一种致命的儿童癌症。我们在患者来源的DIPG培养中进行了化学筛选，同时进行了RNAseq分析和集成计算建模，以确定潜在有效的治疗策略。多组蛋白脱乙酰酶抑制剂Panobinostat在体外和DIPG原位异种移植模型中显示出有效性。Panobinostat与组蛋白去甲基酶抑制剂GSKJ4的联合试验显示有协同作用。综上所述，这些数据提示了一种有前景的DIPG治疗策略。
Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNAseq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated efficacy in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat with histone demethylase inhibitor GSKJ4 revealed synergy. Together, these data suggest a promising therapeutic strategy for DIPG.