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患者来源的类器官在精准肿瘤医学中的应用。

Patient-derived organoids in precision cancer medicine.

机构信息

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Chemical Biology Consortium Sweden, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.

出版信息

Med. 2024 Nov 8;5(11):1351-1377. doi: 10.1016/j.medj.2024.08.010. Epub 2024 Sep 27.

Abstract

Organoids are three-dimensional (3D) cultures, normally derived from stem cells, that replicate the complex structure and function of human tissues. They offer a physiologically relevant model to address important questions in cancer research. The generation of patient-derived organoids (PDOs) from various human cancers allows for deeper insights into tumor heterogeneity and spatial organization. Additionally, interrogating non-tumor stromal cells increases the relevance in studying the tumor microenvironment, thereby enhancing the relevance of PDOs in personalized medicine. PDOs mark a significant advancement in cancer research and patient care, signifying a shift toward more innovative and patient-centric approaches. This review covers aspects of PDO cultures to address the modeling of the tumor microenvironment, including extracellular matrices, air-liquid interface and microfluidic cultures, and organ-on-chip. Specifically, the role of PDOs as preclinical models in gene editing, molecular profiling, drug testing, and biomarker discovery and their potential for guiding personalized treatment in clinical practice are discussed.

摘要

类器官是三维(3D)培养物,通常源自干细胞,可复制人体组织的复杂结构和功能。它们为解决癌症研究中的重要问题提供了一个具有生理相关性的模型。从各种人类癌症中生成患者来源的类器官(PDO)可深入了解肿瘤异质性和空间组织。此外,研究非肿瘤基质细胞增加了研究肿瘤微环境的相关性,从而提高了 PDO 在个性化医学中的相关性。PDO 是癌症研究和患者护理的重大进展,标志着向更具创新性和以患者为中心的方法的转变。这篇综述涵盖了 PDO 培养的各个方面,以解决肿瘤微环境的建模问题,包括细胞外基质、气液界面和微流控培养以及器官芯片。具体讨论了 PDO 作为基因编辑、分子谱分析、药物测试、生物标志物发现的临床前模型的作用及其在指导临床实践中个性化治疗的潜力。

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