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2
Therapeutics: targeting an oncometabolite.治疗方法:靶向一种肿瘤代谢物。
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3
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Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation.靶向抑制白血病细胞中的突变 IDH2 诱导细胞分化。
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An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells.一种突变 IDH1 抑制剂可延缓神经胶质瘤细胞的生长并促进其分化。
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Identification and characterization of a novel mutant isocitrate dehydrogenase 1 inhibitor for glioma treatment.鉴定和表征新型突变体异柠檬酸脱氢酶 1 抑制剂用于治疗神经胶质瘤。
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Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.用小分子突变型异柠檬酸脱氢酶1(IDH1)抑制剂治疗可抑制人软骨肉瘤细胞的致瘤活性并减少致癌代谢物2-羟基戊二酸的产生。
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IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association.异柠檬酸脱氢酶1/2(IDH1/2)而非DNA甲基转移酶3A(DNMT3A)突变是急性髓系白血病患者微小残留病监测的合适靶点:法国急性白血病协会的一项研究
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8
Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications.胆管癌的突变谱分析:预后及治疗意义
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9
Inhibitors of Mutant IDH for the Treatment of Cancer.用于治疗癌症的突变异柠檬酸脱氢酶抑制剂。
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Tumor-suppressive miR148a is silenced by CpG island hypermethylation in IDH1-mutant gliomas.在异柠檬酸脱氢酶1(IDH1)突变型胶质瘤中,肿瘤抑制性miR148a因CpG岛高甲基化而沉默。
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本文引用的文献

1
Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation.靶向抑制白血病细胞中的突变 IDH2 诱导细胞分化。
Science. 2013 May 3;340(6132):622-6. doi: 10.1126/science.1234769. Epub 2013 Apr 4.
2
An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells.一种突变 IDH1 抑制剂可延缓神经胶质瘤细胞的生长并促进其分化。
Science. 2013 May 3;340(6132):626-30. doi: 10.1126/science.1236062. Epub 2013 Apr 4.
3
A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation.异柠檬酸脱氢酶 1(IDH1)R132H/WT 突变导致全基因组 DNA 甲基化改变。
Genome Res. 2012 Dec;22(12):2339-55. doi: 10.1101/gr.132738.111. Epub 2012 Aug 16.
4
Mutant IDH1 is required for IDH1 mutated tumor cell growth.突变型异柠檬酸脱氢酶1(IDH1)是IDH1突变肿瘤细胞生长所必需的。
Oncotarget. 2012 Aug;3(8):774-82. doi: 10.18632/oncotarget.577.
5
IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics.IDH1(R132H) 突变增加了小鼠造血祖细胞并改变了表观遗传学。
Nature. 2012 Aug 30;488(7413):656-9. doi: 10.1038/nature11323.
6
IDH mutation impairs histone demethylation and results in a block to cell differentiation.IDH 突变会损害组蛋白去甲基化,导致细胞分化受阻。
Nature. 2012 Feb 15;483(7390):474-8. doi: 10.1038/nature10860.
7
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype.IDH1 突变足以建立起胶质瘤高甲基化表型。
Nature. 2012 Feb 15;483(7390):479-83. doi: 10.1038/nature10866.
8
Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.白血病 IDH1 和 IDH2 突变导致超甲基化表型,破坏 TET2 功能,并损害造血分化。
Cancer Cell. 2010 Dec 14;18(6):553-67. doi: 10.1016/j.ccr.2010.11.015. Epub 2010 Dec 9.
9
Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma.鉴定出一种 CpG 岛甲基化表型,它定义了神经胶质瘤的一个独特亚群。
Cancer Cell. 2010 May 18;17(5):510-22. doi: 10.1016/j.ccr.2010.03.017. Epub 2010 Apr 15.
10
IDH1 and IDH2 mutations in gliomas.胶质瘤中的异柠檬酸脱氢酶1(IDH1)和异柠檬酸脱氢酶2(IDH2)突变
N Engl J Med. 2009 Feb 19;360(8):765-73. doi: 10.1056/NEJMoa0808710.

释放阻断:用突变 IDH 抑制剂设定分化自由。

Releasing the block: setting differentiation free with mutant IDH inhibitors.

机构信息

The Preston Robert Tisch Brain Tumor Center at Duke, Pediatric Brain Tumor Foundation Institute at Duke, Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Cancer Cell. 2013 May 13;23(5):570-2. doi: 10.1016/j.ccr.2013.04.024.

DOI:10.1016/j.ccr.2013.04.024
PMID:23680144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4465106/
Abstract

Hotspot mutations in IDH1 and IDH2 cause a differentiation block that can promote tumorigenesis. Two recent papers reported that small molecules targeting mutant IDH1 or mutant IDH2 release this differentiation block and/or impede tumor growth, providing a proof-of-concept that mutant IDHs are therapeutically targetable and that their effects are reversible.

摘要

IDH1 和 IDH2 热点突变导致分化阻滞,从而促进肿瘤发生。最近有两篇论文报道,靶向突变 IDH1 或突变 IDH2 的小分子可解除这种分化阻滞和/或抑制肿瘤生长,这为突变 IDH 是可治疗的靶点及其作用是可逆的这一观点提供了证据。