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胶质瘤类器官模型的构建策略、微环境建模及精准治疗应用

英文原题:Construction Strategies, Microenvironmental Modelling and Precision-Therapy Applications of Glioma Organoid Models.

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Construction Strategies, Microenvironmental Modelling and Precision-Therapy Applications of Glioma Organoid Models.

PubMed 2026/08/12(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

胶质瘤,尤其是胶质母细胞瘤,仍然难以建模,因为分子异质性、弥漫性侵袭、血脑屏障和血肿瘤屏障效应、免疫抑制以及反复的治疗逃逸在同一疾病中汇聚。二维培养、胶质瘤干细胞(GSC)系统、急性肿瘤切片和动物模型对于机制研究、药理学和体内验证仍然不可或缺。胶质瘤类器官是补充性研究平台,而非常规诊断或治疗流程的组成部分。本综述将模型构建、微环境验证、治疗扰动和证据分级解读联系起来。

我们比较患者来源的胶质瘤类器官、GSC 来源的类器官、脑类器官-胶质瘤共培养、基因工程脑肿瘤类器官,以及血管相关、含免疫细胞和芯片为基础的平台。

我们区分表型相似性与生理保真度、肿瘤内在药物敏感性与递送能力,以及概念验证活性与已证实的临床效用。我们还审视替莫唑胺耐药、放疗、靶向和联合治疗、抗血管生成治疗、肿瘤电场治疗、免疫细胞治疗、溶瘤病毒、多组学质量控制和前瞻性验证。类器官不应替代动物模型或临床试验。其最站得住脚的作用是提供患者来源的功能层,介于机制、方案排序和分子肿瘤委员会解读之间,而相关主张受限于检测可重复性、临床可达到的暴露量和结局关联。

展开英文摘要原文

Gliomas, and glioblastoma in particular, remain difficult to model because molecular heterogeneity, diffuse invasion, blood-brain and blood-tumour barrier effects, immune suppression and repeated therapeutic escape converge in the same disease.

Two-dimensional cultures, glioma stem cell (GSC) systems, acute tumour slices and animal models remain indispensable for mechanistic research, pharmacology and in vivo validation. Glioma organoids are complementary research platforms, not components of routine diagnostic or treatment procedures. This review links model construction, microenvironmental validation, treatment perturbation and evidence-graded interpretation.

We compare patient-derived glioma organoids, GSC-derived organoids, brain organoid-glioma co-cultures, genetically engineered brain tumour organoids, and vascular-associated, immune-cell-containing and chip-based platforms.

We distinguish phenotypic resemblance from physiological fidelity, tumour-intrinsic drug sensitivity from delivery competence, and proof-of-concept activity from demonstrated clinical utility.

We also examine temozolomide resistance, radiotherapy, targeted and combination therapy, antiangiogenic treatment, tumour-treating fields, immune-cell therapy, oncolytic viruses, multi-omic quality control and prospective validation. Organoids should not substitute for animal models or clinical trials. Their most defensible role is to provide a patient-derived functional layer between mechanism, regimen ranking and molecular tumour-board interpretation, with claims limited by assay reproducibility, clinically achievable exposure and outcome linkage.

论文信息

作者
Chen S、Zhang W、Dai L、Kuang Y、Yang H、Gu J、Peng K、Jiang N
单位
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.China
文献类型
综述
期刊
Cancers2026 Aug 12
原文标识
PubMed 42649915 · DOI 10.3390/cancers18162601