Institute of Molecular Oncology and Stem Cell Biology, Ulm University Hospital, Ulm, Germany.
Department of Urology, Ulm University Hospital, Ulm, Germany.
Expert Opin Drug Discov. 2023 Apr;18(4):429-444. doi: 10.1080/17460441.2023.2194627. Epub 2023 Mar 26.
Pancreatic ductal adenocarcinoma presents with a dismal prognosis. Personalized therapy is urgently warranted to overcome the treatment limitations of the 'one-size-fits-all' scheme. Organoids have emerged as fundamental novel tools to study tumor biology and heterogeneity, hence overcoming limitations of other model systems by better-reflecting tissue heterogeneity and recapitulating in-vivo processes. Besides their crucial role in basic research, they have evolved as tools for translational drug discovery and patient stratification.
This review highlights the achievements of an organoid-based drug investigation and discovery. The authors present an overview of studies using organoids for drug testing. Further, they pinpoint studies correlating the in vitro prediction of organoids to the actual patient`s response. Furthermore, the authors describe novel model systems and take a thorough overlook of microfluidic chips, synthetic matrices, multicellular systems, bioprinting, and stem cell-derived pancreatic organoid systems.
Organoid systems promise great potential for future clinical applications. Indeed, they may be implemented into informed decision-making for guiding therapies. However, validation by randomized trials is mandatory. Additionally, organoids in combination with other cellular compartments may be exploited for drug discovery by studying niche-tumor interaction. Yet, several precautions must be kept in mind, such as standardization and reproducibility.
胰腺导管腺癌预后不良。迫切需要个性化治疗来克服“一刀切”方案的治疗局限性。类器官已成为研究肿瘤生物学和异质性的基本新工具,因此通过更好地反映组织异质性和重现体内过程,克服了其他模型系统的局限性。除了在基础研究中发挥重要作用外,它们还已发展成为用于转化药物发现和患者分层的工具。
本文重点介绍了基于类器官的药物研究和发现方面的成果。作者介绍了使用类器官进行药物测试的研究概述。此外,他们还指出了将类器官的体外预测与实际患者反应相关联的研究。此外,作者还描述了新型模型系统,并对微流控芯片、合成基质、多细胞系统、生物打印和干细胞衍生的胰腺类器官系统进行了全面的考察。
类器官系统为未来的临床应用提供了巨大的潜力。实际上,它们可以用于为指导治疗提供信息的决策中。但是,必须通过随机试验进行验证。此外,通过研究小生境-肿瘤相互作用,类器官与其他细胞区室结合可用于药物发现。然而,必须牢记一些预防措施,例如标准化和可重复性。