Deciphering the multifaceted roles and clinical implications of 2-hydroxyglutarate in cancer

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research Pub Date : 2024-09-29 DOI:10.1016/j.phrs.2024.107437

Jie Hao , Ziyi Huang , Siyue Zhang , Kefan Song , Juncheng Wang , Chao Gao , Zhiqing Fang , Ning Zhang

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引用次数: 0

Abstract

Increasing evidence indicates that 2-hydroxyglutarate (2HG) is an oncometabolite that drives tumour formation and progression. Due to mutations in isocitrate dehydrogenase (IDH) and the dysregulation of other enzymes, 2HG accumulates significantly in tumour cells. Due to its structural similarity to α-ketoglutarate (αKG), accumulated 2HG leads to the competitive inhibition of αKG-dependent dioxygenases (αKGDs), such as KDMs, TETs, and EGLNs. This inhibition results in epigenetic alterations in both tumour cells and the tumour microenvironment. This review comprehensively discusses the metabolic pathways of 2HG and the subsequent pathways influenced by elevated 2HG levels. We will delve into the molecular mechanisms by which 2HG exerts its oncogenic effects, particularly focusing on epigenetic modifications. This review will also explore the various methods available for the detection of 2HG, emphasising both current techniques and emerging technologies. Furthermore, 2HG shows promise as a biomarker for clinical diagnosis and treatment. By integrating these perspectives, this review aims to provide a comprehensive overview of the current understanding of 2HG in cancer biology, highlight the importance of ongoing research, and discuss future directions for translating these findings into clinical applications.

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解密 2-羟基戊二酸在癌症中的多方面作用和临床意义。

越来越多的证据表明，2-羟基戊二酸（2HG）是一种促进肿瘤形成和发展的代谢产物。由于异柠檬酸脱氢酶（IDH）的突变和其他酶的失调，2HG在肿瘤细胞中大量积累。由于其结构与α-酮戊二酸（αKG）相似，累积的2HG会导致依赖αKG的二氧酶（αKGDs），如KDMs、TETs和EGLNs受到竞争性抑制。这种抑制会导致肿瘤细胞和肿瘤微环境发生表观遗传学改变。本综述将全面讨论 2HG 的代谢途径以及受 2HG 水平升高影响的后续途径。我们将深入探讨 2HG 发挥致癌作用的分子机制，尤其侧重于表观遗传修饰。本综述还将探讨可用于检测 2HG 的各种方法，重点关注现有技术和新兴技术。此外，2HG有望成为临床诊断和治疗的生物标记物。通过整合这些观点，本综述旨在全面概述目前对癌症生物学中 2HG 的理解，强调正在进行的研究的重要性，并讨论将这些发现转化为临床应用的未来方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.