Evolution of Preclinical Models for Glioblastoma Modelling and Drug Screening.

IF 4.7 2区 医学 Q1 ONCOLOGY
Current Oncology Reports Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI:10.1007/s11912-025-01672-4
Grace Thomas, Ruman Rahman
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引用次数: 0

Abstract

Purpose of review: Isocitrate dehydrogenase wild-type glioblastoma is an extremely aggressive and fatal primary brain tumour, characterised by extensive heterogeneity and diffuse infiltration of brain parenchyma. Despite multimodal treatment and diverse research efforts to develop novel therapies, there has been limited success in improving patient outcomes. Constructing physiologically relevant preclinical models is essential to optimising drug screening processes and identifying more effective treatments.

Recent findings: Traditional in-vitro models have provided critical insights into glioblastoma pathophysiology; however, they are limited in their ability to recapitulate the complex tumour microenvironment and its interactions with surrounding cells. In-vivo models offer a more physiologically relevant context, but often do not fully represent human pathology, are expensive, and time-consuming. These limitations have contributed to the low translational success of therapies from trials to clinic. Organoid and glioblastoma-on-a-chip technology represent significant advances in glioblastoma modelling and enable the replication of key features of the human tumour microenvironment, including its structural, mechanical, and biochemical properties. Organoids provide a 3D system that captures cellular heterogeneity and tumour architecture, while microfluidic chips offer dynamic systems capable of mimicking vascularisation and nutrient exchange. Together, these technologies hold tremendous potential for high throughput drug screening and personalised, precision medicine. This review explores the evolution of preclinical models in glioblastoma modelling and drug screening, emphasising the transition from traditional systems to more advanced organoid and microfluidic platforms. Furthermore, it aims to evaluate the advantages and limitations of both traditional and next-generation models, investigating their combined potential to address current challenges by integrating complementary aspects of specific models and techniques.

胶质母细胞瘤模型和药物筛选的临床前模型的发展。
综述目的:异柠檬酸脱氢酶野生型胶质母细胞瘤是一种极具侵袭性和致死性的原发性脑肿瘤,其特点是广泛的异质性和脑实质弥漫性浸润。尽管多模式治疗和开发新疗法的各种研究努力,但在改善患者预后方面取得的成功有限。构建生理学相关的临床前模型对于优化药物筛选过程和确定更有效的治疗方法至关重要。最近的发现:传统的体外模型为胶质母细胞瘤的病理生理提供了重要的见解;然而,它们在概括复杂的肿瘤微环境及其与周围细胞的相互作用方面的能力有限。体内模型提供了更相关的生理背景,但往往不能完全代表人类病理,昂贵且耗时。这些限制导致了从试验到临床治疗的低转化成功率。类器官和胶质母细胞瘤芯片技术在胶质母细胞瘤建模方面取得了重大进展,并能够复制人类肿瘤微环境的关键特征,包括其结构、机械和生化特性。类器官提供了一个3D系统,可以捕获细胞异质性和肿瘤结构,而微流控芯片提供了能够模拟血管化和营养交换的动态系统。总之,这些技术在高通量药物筛选和个性化精准医疗方面具有巨大的潜力。这篇综述探讨了胶质母细胞瘤建模和药物筛选的临床前模型的发展,强调了从传统系统到更先进的类器官和微流体平台的转变。此外,它旨在评估传统模型和下一代模型的优点和局限性,通过集成特定模型和技术的互补方面来研究它们的综合潜力,以解决当前的挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.50
自引率
0.00%
发文量
187
审稿时长
6-12 weeks
期刊介绍: This journal aims to review the most important, recently published clinical findings in the field of oncology. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care of those affected by cancer. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as cancer prevention, leukemia, melanoma, neuro-oncology, and palliative medicine. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.
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