胶质母细胞瘤耐药的基本信号通路和开发药物发现的强大类器官模型

Athira Pratap, Eun‐Jung Lim, I. Kwak, Byoung-San Moon
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摘要

本文就胶质母细胞瘤耐药的分子机制作一综述。随着越来越多的研究继续探索治疗胶质母细胞瘤的新方法,从使用类器官模型进行药物筛选到开发新的细胞疗法,了解使胶质母细胞瘤难以治疗的基本分子景观至关重要。本文对常规化疗替莫唑胺的耐药途径进行了探讨。考虑DNA修复途径、p53介导的细胞凋亡和自噬、趋同增殖途径和表观遗传机制,为开发复杂的药物靶点和联合治疗提供了途径。最后,本文重点介绍了这些机制,并为未来基于类器官的药物筛选提供了参考材料。
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Fundamental signaling pathways for glioblastoma drug resistance and developing robust organoid models for drug discovery
This article presents a review of the current literature on the molecular mechanisms of treatment resistance in glioblastoma. As mounting research continues to explore novel methods of treating glioblastoma, from using organoid models for drug screening to developing novel cellular therapies, it is critical to understand the fundamental molecular landscape that makes glioblastoma difficult to treat. This review explores the means of chemoresistance to the conventional chemotherapy temozolomide. Consideration of DNA repair pathways, p53-mediated apoptosis and autophagy, convergent proliferation pathways, and epigenetic mechanisms demonstrate avenues for the development of sophisticated drug targets and combination treatments. Ultimately, this article highlights each of these mechanisms and presents referential material for future endeavors in organoid-based drug screening.
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