Izquierdo Cristina, Joubert Bastien, Ducray François
aHospices Civils de Lyon, Groupe Hospitalier Est, Service de Neuro-Oncologie, Lyon, France bUnit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO L'Hospitalet-IDIBELL, Barcelona, Spain cUniversité Claude Bernard Lyon 1 dDepartment of Cancer Cell Plasticity, Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, Lyon, France.
Curr Opin Oncol. 2017 Nov;29(6):434-442. doi: 10.1097/CCO.0000000000000409.
The current review summarizes recent advances on the oncogenesis, classification and treatment of adult anaplastic gliomas.
According to the 2016 WHO classification, three main molecular subgroups of adult diffuse anaplastic gliomas can be distinguished based on the 1p/19q codeletion and isocitrate dehydrogenase (IDH) mutation status. In the future, this classification may be further refined based on the telomerase reverse transcriptase promoter and alpha thalassemia/mental retardation syndrome X-linked mutation status, gene expression, DNA methylation and genomic profiling. Both newly diagnosed 1p/19q codeleted and 1p/19q-intact anaplastic gliomas benefit from the addition of chemotherapy to radiotherapy. However, in 1p/19q codeleted anaplastic gliomas, Procarbazine, CCNU and Vincristine chemotherapy seems more effective than temozolomide. At recurrence, 1p/19q-intact anaplastic gliomas do not benefit from the addition of bevacizumab to temozolomide. The use of poly(adenosine 5'-diphosphate-ribose) inhibitors may be another way of specifically targeting IDH-mutant gliomas in addition to specific inhibitors, demethylating agents and anti-IDH vaccines. v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutant anaplastic xanthoastrocytomas and gangliogliomas may benefit from BRAF and mitogen-activated protein kinase inhibitors.
Molecular characterization is mandatory for integrated diagnosis and appropriate management of adult anaplastic gliomas. Both 1p/19q codeleted and 1p/19q-intact anaplastic diffuse gliomas benefit from early chemotherapy. At recurrence, preliminary data suggest a potential role for targeted therapies in specific molecular subgroups.
本综述总结了成人间变性胶质瘤在肿瘤发生、分类和治疗方面的最新进展。
根据2016年世界卫生组织分类，可基于1p/19q共缺失和异柠檬酸脱氢酶（IDH）突变状态区分成人弥漫性间变性胶质瘤的三个主要分子亚组。未来，该分类可能会根据端粒酶逆转录酶启动子和X连锁的α地中海贫血/智力发育迟缓综合征突变状态、基因表达、DNA甲基化和基因组分析进一步细化。新诊断的1p/19q共缺失和1p/19q完整的间变性胶质瘤都能从放疗联合化疗中获益。然而，在1p/19q共缺失的间变性胶质瘤中，丙卡巴肼、洛莫司汀和长春新碱化疗似乎比替莫唑胺更有效。复发时，1p/19q完整的间变性胶质瘤在替莫唑胺基础上加用贝伐单抗并无益处。除了特异性抑制剂、去甲基化剂和抗IDH疫苗外，使用聚（腺苷5'-二磷酸-核糖）抑制剂可能是另一种特异性靶向IDH突变型胶质瘤的方法。v-raf鼠肉瘤病毒癌基因同源物B1（BRAF）突变的间变性黄色星形细胞瘤和神经节胶质瘤可能从BRAF和丝裂原活化蛋白激酶抑制剂中获益。
分子特征对于成人间变性胶质瘤的综合诊断和适当管理至关重要。1p/19q共缺失和1p/19q完整的间变性弥漫性胶质瘤都能从早期化疗中获益。复发时，初步数据表明靶向治疗在特定分子亚组中可能发挥作用。
