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胶质母细胞瘤治疗的个性化:外植体类器官的应用、挑战及未来展望

Personalising glioblastoma medicine: explant organoid applications, challenges and future perspectives.

作者信息

Skarne Niclas, D'Souza Rochelle C J, Palethorpe Helen M, Bradbrook Kylah A, Gomez Guillermo A, Day Bryan W

机构信息

Sid Faithfull Brain Cancer Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

School of Biomedical Sciences and Faculty of Medicine, The University of Queensland, Brisbane, 4072, Australia.

出版信息

Acta Neuropathol Commun. 2025 Jan 11;13(1):6. doi: 10.1186/s40478-025-01928-x.

Abstract

Glioblastoma (GBM) is a highly aggressive adult brain cancer, characterised by poor prognosis and a dismal five-year survival rate. Despite significant knowledge gains in tumour biology, meaningful advances in patient survival remain elusive. The field of neuro-oncology faces many disease obstacles, one being the paucity of faithful models to advance preclinical research and guide personalised medicine approaches. Recent technological developments have permitted the maintenance, expansion and cryopreservation of GBM explant organoid (GBO) tissue. GBOs represent a translational leap forward and are currently the state-of-the-art in 3D in vitro culture system, retaining brain cancer heterogeneity, and transiently maintaining the immune infiltrate and tumour microenvironment (TME). Here, we provide a review of existing brain cancer organoid technologies, in vivo xenograft approaches, evaluate in-detail the key advantages and limitations of this rapidly emerging technology, and consider solutions to overcome these difficulties. GBOs currently hold significant promise, with the potential to emerge as the key translational tool to synergise and enhance next-generation omics efforts and guide personalised medicine approaches for brain cancer patients into the future.

摘要

胶质母细胞瘤(GBM)是一种侵袭性很强的成人大脑癌症,其特点是预后不良,五年生存率很低。尽管在肿瘤生物学方面取得了重大知识进展,但患者生存率的显著提高仍然难以实现。神经肿瘤学领域面临许多疾病方面的障碍,其中之一是缺乏可靠的模型来推进临床前研究和指导个性化医疗方法。最近的技术发展使得GBM外植体类器官(GBO)组织能够得以维持、扩增和冷冻保存。GBO代表了一个向前的转化性飞跃,并且是目前三维体外培养系统中的最先进技术,保留了脑癌的异质性,并暂时维持免疫浸润和肿瘤微环境(TME)。在此,我们综述了现有的脑癌类器官技术、体内异种移植方法,详细评估了这种迅速兴起的技术的关键优势和局限性,并考虑了克服这些困难的解决方案。GBO目前具有重大前景,有可能成为协同和加强下一代组学研究工作以及指导未来脑癌患者个性化医疗方法的关键转化工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac40/11724554/295277e740b6/40478_2025_1928_Fig1_HTML.jpg

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