Reitman Zachary J, Winkler Frank, Elia Andrew E H
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Harvard Radiation Oncology Program, Boston, Massachusetts.
Semin Neurol. 2018 Feb;38(1):50-61. doi: 10.1055/s-0038-1623534. Epub 2018 Mar 16.
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis. Here, we review these molecular features and discuss major clinical trials that have recently defined the field. We describe genetic alterations in isocitrate dehydrogenase, ATRX, the telomerase promoter, and histone H3 variants that promote GBM tumorigenesis and have altered GBM categorization. We also discuss intratumoral genetic heterogeneity as one explanation for therapeutic failures and explain how ultra-long extensions of glioma cells, called tumor microtubes, mediate therapeutic resistance. These findings provide new insights into GBM biology and offer hope for the development of next-generation therapies.
胶质母细胞瘤（GBM）是中枢神经系统最常见的原发性恶性肿瘤。目前GBM的标准治疗方案是最大限度地切除肿瘤，随后进行术后放疗，并同步及辅助使用替莫唑胺。尽管采用了这种多模态治疗方法，GBM的中位生存期仍仅略高于1年。在过去十年中，全基因组分析揭示了GBM的新分子特征，这些特征完善了其分类，并为GBM发病机制的分子基础提供了新的见解。在此，我们回顾这些分子特征，并讨论最近界定该领域的主要临床试验。我们描述了异柠檬酸脱氢酶、ATRX、端粒酶启动子和组蛋白H3变体中的基因改变，这些改变促进了GBM的肿瘤发生并改变了GBM的分类。我们还讨论了肿瘤内基因异质性作为治疗失败的一种解释，并解释了被称为肿瘤微管的胶质瘤细胞超长延伸如何介导治疗抗性。这些发现为GBM生物学提供了新的见解，并为下一代治疗方法的开发带来了希望。
