异柠檬酸脱氢酶基因突变在软骨肉瘤中的研究进展及展望

Research Progress and Prospects of Isocitrate Dehydrogenase Gene Mutation in Chondrosarcoma

人类代谢基因中异柠檬酸脱氢酶(IDH)是较易发生突变的基因。在烟酰胺腺嘌呤二核苷酸磷酸(NADPH)的作用下,突变的IDH可与α-酮戊二酸(α-KG)结合并将其还原为2-羟基戊二酸(2-HG),参与肿瘤发生的多种生物过程。IDH在脑胶质瘤及急性髓系白血病中研究较多,在软骨肉瘤中的研究甚少。软骨肉瘤中存在IDH基因高频突变,易出现复发和转移,复发或转移后治疗方案有限,患者预后较差,临床迫切需要寻找新的治疗方案。本文就IDH基因突变在软骨肉瘤发生、预后、鉴别诊断及治疗中的作用予以综述,通过进一步阐述IDH基因突变在软骨肉瘤发生、发展中的生物学作用,并对强效的IDH抑制剂及抗癌药物研发进行展望,为临床治疗方案的制订及预后判断提供参考依据。

Isocitrate dehydrogenase(IDH)is the more mutation-prone human metabolic gene.In the presence of nicotinamide adenine dinucleotide phosphate(NADPH),mutant IDH can bind toα-ketoglutaric acid(α-KG)and reduce it to 2-hydroxyglutaric acid(2-HG),participating in various biological processes of tumorigenesis.IDH has been widely studied in glioma and acute myeloid leukemia,and rarely in chondrosarcoma.Chondrosarcoma is prone to recurrence and metastasis due to the presence of high-frequency mutations in the IDH gene,and treatment options are limited after recurrence or metastasis,resulting in a poor prognosis for patients and an urgent clinical need to find new treatment options.This article reviews the role of IDH mutations in the development,prognosis,differential diagnosis and treatment of chondrosarcoma,further elaborates the biological role of IDH gene mutation in the occurrence and development of chondrosarcoma,and provides an outlook on the development of powerful IDH inhibitors and anti-cancer drugs,in order to provide a reference for the establishment of therapeutic regimen and prognostic evaluation.