Organoid Models of Glioblastoma and Their Role in Drug Discovery.
Organoid Models of Glioblastoma and Their Role in Drug Discovery.
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DOI：
10.3389/fncel.2021.605255
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发表时间：
2021
影响因子：
5.3
通讯作者：
Zeier Z
中科院分区：
文献类型：
--
作者：
Rybin MJ;Ivan ME;Ayad NG;Zeier Z
胶质母细胞瘤（GBM）是一种毁灭性的成人脑癌，具有高复发率和治疗耐药性。细胞异质性和周围脑组织的广泛侵袭是 GBM 的特征，导致其难以治疗。目前的 GBM 模型系统没有概括 GBM 的一些复杂特征，也没有产生足够有效的治疗方法。这让人们对当前 GBM 模型和药物发现范式的有效性产生了怀疑。为了寻找替代的临床前 GBM 模型，已经使用人体细胞开发了各种基于 3D 类器官的 GBM 模型系统。这些系统的可扩展性以及更准确地模拟 GBM 特征的潜力，为临床前 GBM 研究和药物发现工作提供了有前景的新途径。在这里，我们回顾了当前的类器官 GBM 模型套件、它们各自的优点和缺点，并讨论了它们未来的应用，重点是化合物筛选。
Glioblastoma (GBM) is a devastating adult brain cancer with high rates of recurrence and treatment resistance. Cellular heterogeneity and extensive invasion of surrounding brain tissues are characteristic features of GBM that contribute to its intractability. Current GBM model systems do not recapitulate some of the complex features of GBM and have not produced sufficiently-effective treatments. This has cast doubt on the effectiveness of current GBM models and drug discovery paradigms. In search of alternative pre-clinical GBM models, various 3D organoid-based GBM model systems have been developed using human cells. The scalability of these systems and potential to more accurately model characteristic features of GBM, provide promising new avenues for pre-clinical GBM research and drug discovery efforts. Here, we review the current suite of organoid-GBM models, their individual strengths and weaknesses, and discuss their future applications with an emphasis on compound screening.
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