Mukasa Akitake
Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University.
No Shinkei Geka. 2022 Jan;50(1):8-18. doi: 10.11477/mf.1436204527.
Several important revisions were made regarding the classification of brain tumors in the newest version(5th edition)of the WHO classification of tumours of the central nervous system published in 2021. Now, most so-called "lower-grade glioma(s)" fall into the category of IDH-mutant diffuse glioma, represented by astrocytoma and oligodendroglioma. For the diagnosis of these IDH-mutant gliomas, the determination of genetic alterations in /, , chromosome 1p/19q, , promoter, and / is important. Generally, in addition to the mutation, astrocytomas have mutation and mutation, whereas oligodendrogliomas have 1p/19q codeletion and promoter mutation. For tumor grading in the new WHO classification, astrocytomas harboring / homozygous deletion can be categorized as WHO grade 4 astrocytomas, even though they do not have microvascular proliferation or necrosis. For these IDH-mutant tumors, molecular targeted therapy for IDH mutation has been under development. Several enzymatic inhibitors of IDH1/2 have been tested in clinical trials and were suggested to have some clinical effectiveness. Currently, large-scale trials are ongoing. Besides these inhibitors, other strategies for targeting IDH mutations, such as immunotherapy and therapy targeting aberrant metabolic pathways resulting from IDH mutation are also examined. These novel therapies will be beneficial to patients.
2021年发布的世界卫生组织中枢神经系统肿瘤分类最新版(第5版)对脑肿瘤的分类进行了多项重要修订。如今,大多数所谓的“低级别胶质瘤”属于异柠檬酸脱氢酶(IDH)突变型弥漫性胶质瘤范畴,以星形细胞瘤和少突胶质细胞瘤为代表。对于这些IDH突变型胶质瘤的诊断,确定IDH、1p/19q染色体、TERT启动子以及ATRX的基因改变很重要。一般来说,除了IDH突变外,星形细胞瘤还存在TP53突变和ATRX突变,而少突胶质细胞瘤则有1p/19q共缺失和TERT启动子突变。在世界卫生组织新分类中进行肿瘤分级时,携带TERT/TERT纯合缺失的星形细胞瘤可归类为世界卫生组织4级星形细胞瘤,即便它们没有微血管增殖或坏死。对于这些IDH突变型肿瘤,针对IDH突变的分子靶向治疗一直在研发中。几种IDH1/2酶抑制剂已在临床试验中进行测试,并显示出一定的临床疗效。目前,大规模试验正在进行。除了这些抑制剂外,其他针对IDH突变的策略,如免疫治疗以及针对IDH突变导致的异常代谢途径的治疗也在研究中。这些新型疗法将对患者有益。