异柠檬酸脱氢酶抑制剂在脑胶质瘤治疗中的研究进展
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国家自然科学基金( 82173032,82203682);辽宁省科技计划联合计划(基金)项目(2023JH2/101700156);沈阳市科技计划( 22-321-33-50);“ 医一工交叉研究基金”项目( LD202503)


Research progress of IDH inhibitors for glioma treatment
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    摘要:

    脑胶质瘤是成人最常见的原发性脑恶性肿瘤,通过现有治疗手段难以治愈。异柠檬 酸脱氢酶(IDH)突变型脑胶质瘤在分子水平方面表现出异质性,突变的IDH基因产物D-2-羟基戊二 酸(D-2-HG)促使DNA超甲基化和免疫干扰,进而促进肿瘤生长。近年来,IDH抑制剂如Ivosidenib 和 Vorasidenib 在临床前模型和早期临床试验中展现出能够降低D-2-HG 水平并诱导细胞分化的效果。 Ⅲ期INDIGO 试验显示,Vorasidenib 能够显著延长非增强2 级IDH突变脑胶质瘤患者无进展生存期,并 于2024 年获得FDA 批准。现详细介绍IDH抑制剂在脑胶质瘤治疗中的进展,其作为一种耐受性良好的 治疗方案,对特定患者群体有益,未来结合新药物和联合疗法的研究可能进一步拓展其治疗潜力。

    Abstract:

    Glioma is the most common primary malignant brain tumor in adults and is difficult to cure with current treatment methods. Isocitrate dehydrogenase( IDH) mutant gliomas exhibit molecular heterogeneity. The mutated IDH gene product D-2-Hydroxyglutarate( D-2-HG) promotes DNA hypermethylation and immune suppression thereby driving tumor growth. In recent years, IDH inhibitors such as Ivosidenib and Vorasidenib have demonstrated the ability to reduce D-2-HG levels and induce cellular differentiation in preclinical models and early-phase clinical trials. The Phase Ⅲ INDIGO trial demonstrates that Vorasidenib significantly prolongs progression-free survival in patients with non-amplified grade 2 IDH mutant gliomas, and receives FDA approval in 2024. This paper provides a detailed overview of the progress of IDH inhibitors for gliomas treatment, highlighting their role as a well-tolerated therapeutic option that offers benefits for selected patient populations. Future research combining novel drugs and combination therapies may further expand its therapeutic potential.

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史记,石杰,许会哲,王秋月,刘强,孙佩欣,张烨,姚冰,朴浩哲.异柠檬酸脱氢酶抑制剂在脑胶质瘤治疗中的研究进展[J].神经疾病与精神卫生,2025,25(12):837-845
DOI :10.3969/j. issn.1009-6574.2025.12.001.

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  • 在线发布日期: 2025-12-15