New Directions in the Treatment of Glioblastoma
New Directions in the Treatment of Glioblastoma
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DOI：
10.1055/s-0038-1623534
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发表时间：
2018-02-01
影响因子：
2.7
通讯作者：
Elia, Andrew E. H.
中科院分区：
文献类型：
--
作者：
Reitman, Zachary J.;Winkler, Frank;Elia, Andrew E. H.
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的标准治疗是最大限度切除，然后进行术后放疗，同时使用替莫唑胺作为辅助治疗。尽管有这种多模式治疗，GBM的中位生存期仍略高于1年。在过去的十年中，全基因组分析已经发现了GBM的新分子特征，这些特征已经完善了GBM的分类，并为GBM发病机制的分子基础提供了新的见解。在这里，我们回顾了这些分子特征，并讨论了最近定义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变异体的遗传改变，这些变异体促进GBM肿瘤发生并改变了GBM分类。我们还讨论了肿瘤内遗传异质性作为治疗失败的一种解释，并解释了胶质瘤细胞的超长延伸（称为肿瘤微管）如何介导治疗耐药性。这些发现为GBM生物学提供了新的见解，并为下一代疗法的开发提供了希望。
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.