Translational Neuro-Oncology Laboratory, Department of Neurosurgery, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA; Department of Neurosurgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany; Division of Pediatric Neuro-Oncogenomics, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) - partner site Essen/Düsseldorf, Düsseldorf, Germany; Institute of Neuropathology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
Pharmacol Ther. 2018 Feb;182:70-79. doi: 10.1016/j.pharmthera.2017.08.006. Epub 2017 Aug 19.
High-grade gliomas (HGG) are the most common malignant brain tumors in the pediatric population and account for a large subset of all pediatric central nervous system neoplasms. The management of pediatric HGG continues to be challenging, with poor outcome in many cases despite aggressive treatments. Consequently, parallel research efforts have been focused on identifying the underlying genetic and biological basis of pediatric HGG in order to more clearly define prognostic subgroups for treatment stratification as well as identify new treatment targets. These cutting-edge advances have revolutionized pediatric neuro-oncology and have revealed novel oncogenic vulnerabilities that are being therapeutically leveraged. Promising treatments - including pathway-targeting small molecules as well as epigenetic therapy - are being evaluated in clinical trials, and recent genomic discoveries in rare glioma subgroups have led to the identification of additional new potentially-actionable alterations. This review summarizes the current state of knowledge about the molecular characterization of pediatric HGG in correlation to the revised World Health Organization (WHO) classification, as well as provides an overview of some targeted treatment approaches in the modern clinical management of high-grade gliomas.
高级别胶质瘤（HGG）是儿童中最常见的恶性脑肿瘤，占所有儿童中枢神经系统肿瘤的很大一部分。尽管采用了积极的治疗方法，但儿童 HGG 的治疗仍然具有挑战性，许多情况下预后不良。因此，平行的研究工作一直致力于确定儿童 HGG 的潜在遗传和生物学基础，以便更清楚地定义治疗分层的预后亚组，并确定新的治疗靶点。这些前沿进展彻底改变了儿科神经肿瘤学，并揭示了正在治疗中利用的新致癌弱点。有前途的治疗方法——包括靶向通路的小分子和表观遗传疗法——正在临床试验中进行评估，而罕见胶质瘤亚组的最近基因组发现导致了其他潜在可操作改变的鉴定。这篇综述总结了目前关于儿科 HGG 的分子特征与修订后的世界卫生组织（WHO）分类之间的相关性的知识状态，并概述了现代高级别胶质瘤临床管理中的一些靶向治疗方法。
