The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response. IDH mutations have been associated with tumor development and progression in various solid tumors such as glioma, cholangiocarcinoma, chondrosarcoma, and other tumor types and have become crucial markers in molecular classification and prognostic assessment. The intratumoral and serum levels of D-2-hydroxyglutarate (D-2-HG) could serve as diagnostic biomarkers for identifying IDH mutant (IDHmut) tumors. As a result, an increasing number of clinical trials are evaluating targeted treatments for IDH1/IDH2 mutations. Recent studies have shown that the focus of these new therapeutic strategies is not only the neomorphic activity of the IDHmut enzymes but also the epigenetic shift induced by IDH mutations and the potential role of combination treatments. Here, we provide an overview of the current knowledge about IDH mutations in solid tumors, with a particular focus on available IDH-targeted treatments and emerging results from clinical trials aiming to explore IDHmut tumor-specific features and to identify the clinical benefit of IDH-targeted therapies and their combination strategies. An insight into future perspectives and the emerging roles of circulating biomarkers and radiomic features is also included.
异柠檬酸脱氢酶1和2（IDH1和IDH2）参与人体细胞的关键代谢过程，调控细胞分化、增殖及氧化损伤反应。IDH突变与胶质瘤、胆管癌、软骨肉瘤等多种实体肿瘤的发生发展密切相关，已成为分子分型与预后评估的重要标志物。肿瘤组织及血清中的D-2-羟基戊二酸（D-2-HG）水平可作为识别IDH突变型肿瘤的诊断性生物标志物。因此，越来越多的临床试验正在评估针对IDH1/IDH2突变的靶向治疗。最新研究表明，这些新型治疗策略不仅关注IDH突变酶的新形态活性，更着眼于IDH突变诱导的表观遗传学改变及联合治疗的潜在价值。本文系统综述当前关于实体肿瘤中IDH突变的研究进展，重点探讨现有IDH靶向治疗方案及临床试验成果，旨在揭示IDH突变型肿瘤的特异性特征，评估IDH靶向治疗及其联合策略的临床获益。同时展望未来研究方向，并探讨循环生物标志物与影像组学特征的新兴应用价值。
Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives
肿瘤(癌症)患者之家