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.

中文翻译：

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间充质转化：胶质母细胞瘤发病机制和治疗耐药性的罗塞塔石碑

尽管经过数十年的研究，胶质母细胞瘤（GBM）在所有形式的癌症中仍然是致命的。肿瘤间和肿瘤内的高度异质性及其生物学位置（大脑）是有效治疗的主要障碍。分子和单细胞分析可识别具有不同预后的不同分子亚型，而同一肿瘤中可以存在多种亚型。不同亚型之间对治疗或复发期间的细胞可塑性增加了 GBM 治疗的另一个障碍。这种表型转变是通过肿瘤本身或微环境因素内多个途径的激活来诱导和维持的。在这篇综述中，GBM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，同时重点讨论了研究这把动态双刃剑的新兴工具和方法。