Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance.

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance.
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DOI:
10.1002/advs.202002015
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发表时间:
2020-11
期刊:
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子:
--
通讯作者:
Tannous BA
Tannous BA
中科院分区:
其他
文献类型:
--
作者:
Azam Z;To ST;Tannous BA

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尽管经过几十年的研究,胶质母细胞瘤(GBM)仍然是所有形式的癌症中的致命性。肿瘤间和肿瘤内的高度异质性及其生物学位置(大脑)沿着是有效治疗的主要障碍。分子和单细胞分析鉴定具有不同预后的不同分子亚型,而多种亚型可以存在于同一肿瘤中。不同亚型对治疗的反应或复发期间的细胞可塑性增加了GBM治疗的另一个障碍。这种表型转变是由肿瘤本身或微环境因素内的几种途径的激活诱导和维持的。在这篇综述中,GBM中细胞变化的动态性质以及肿瘤(免疫)微环境如何塑造这一过程导致治疗耐药性,同时强调研究这把动态双刃剑的新兴工具和方法。这篇综述总结了胶质母细胞瘤细胞转移的动态性质,以及肿瘤(免疫)微环境如何塑造这一过程导致治疗耐药性,同时强调了研究这把动态双刃剑的新兴工具和方法。
Despite decades of research, glioblastoma (GBM) remains invariably fatal among all forms of cancers. The high level of inter‐ and intratumoral heterogeneity along with its biological location, the brain, are major barriers against effective treatment. Molecular and single cell analysis identifies different molecular subtypes with varying prognosis, while multiple subtypes can reside in the same tumor. Cellular plasticity among different subtypes in response to therapies or during recurrence adds another hurdle in the treatment of GBM. This phenotypic shift is induced and sustained by activation of several pathways within the tumor itself, or microenvironmental factors. In this review, the dynamic nature of cellular shifts in GBM and how the tumor (immune) microenvironment shapes this process leading to therapeutic resistance, while highlighting emerging tools and approaches to study this dynamic double‐edged sword are discussed. This review summarizes the dynamic nature of cellular shift in glioblastoma and how the tumor (immune) microenvironment shapes this process leading to therapeutic resistance, while highlighting emerging tools and approaches to study this dynamic double‐edged sword.
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