针对小儿高级别胶质瘤停滞的表观遗传发育程序的分化治疗。

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research Pub Date : 2025-02-01 DOI:10.1016/j.phrs.2025.107599

Wang Xiang , Xiaolin Zhang , Minhai Dong , Lijun Wan , Bin Zhang , Feng Wan

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引用次数: 0

摘要

小儿高级别胶质瘤（pHGGs）是儿童中最常见的脑恶性肿瘤，其特征是分化受阻。pHGGs的表观遗传格局，特别是h3k27改变和h3g34突变亚型，表明这些肿瘤可能特别容易受到靶向阻断分化策略的影响。分化治疗旨在通过促进胶质瘤细胞分化为更成熟和恶性程度更低的细胞来克服这种分化阻断。表观遗传调节剂，包括组蛋白去乙酰化酶（HDAC）抑制剂、zeste同源物2增强剂（EZH2）、BRG1/ brm相关因子（BAF）复合物，通过改变胶质瘤细胞的分化程序，在pHGGs的临床前研究中显示出前景。尽管在克服肿瘤细胞异质性方面仍存在挑战，诱导分化疗法有望治疗目前无法治愈的儿童脑癌。

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Differentiation therapy targeting the stalled epigenetic developmental programs in pediatric high-grade gliomas

Pediatric high-grade gliomas (pHGGs) are the most common brain malignancies in children and are characterized by blocked differentiation. The epigenetic landscape of pHGGs, particularly the H3K27-altered and H3G34-mutant subtypes, suggests these tumors may be particularly susceptible to strategies that target blocked differentiation. Differentiation therapy aims to overcome this differentiation blockade by promoting glioma cell differentiation into more mature and less malignant cells. Epigenetic modulators, including inhibitors of histone deacetylase (HDAC), enhancer of zeste homolog 2 (EZH2), BRG1/BRM-associated factor (BAF) complex, have shown promise in preclinical studies of pHGGs by altering the differentiation program of glioma cells. Although challenges remain in overcoming tumor cell heterogeneity, induced differentiation therapy holds promise for treating these currently incurable pediatric brain cancers.

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来源期刊

Pharmacological research 医学-药学

CiteScore

18.70

自引率

3.20%

发文量

491

审稿时长

8 days

期刊介绍： Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.