Background

Pancreatic ductal adenocarcinoma has the lowest survival rate among all major cancers and is the third leading cause of cancer-related mortality. The stagnant survival statistics and dismal response rates to current therapeutics highlight the need for more efficient preclinical models. Patient-derived organoids (PDOs) offer new possibilities as powerful preclinical models able to account for interpatient variability. Organoid development can be divided into four different key phases: establishment, propagation, drug screening and response prediction. Establishment entails tailored tissue extraction and growth protocols, propagation requires consistent multiplication and passaging, while drug screening and response prediction will benefit from shorter and more precise assays, and clear decision-making tools.

Conclusions

This review attempts to outline the most important challenges that remain in exploiting organoid platforms for drug discovery and clinical applications. Some of these challenges may be overcome by novel methods that are under investigation, such as 3D bioprinting systems, microfluidic systems, optical metabolic imaging and liquid handling robotics. We also propose an optimized organoid workflow inspired by all technical solutions we have presented.

中文翻译：

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用于个体化胰腺癌治疗的类器官技术

 背景

胰腺导管腺癌在所有主要癌症中生存率最低，是癌症相关死亡率的第三大原因。停滞的生存统计数据和对当前治疗方法的低反应率凸显了对更有效的临床前模型的需求。患者来源的类器官（PDO）作为强大的临床前模型提供了新的可能性，能够解释患者间的变异性。类器官的发育可分为四个不同的关键阶段：建立、繁殖、药物筛选和反应预测。建立需要定制的组织提取和生长方案，繁殖需要一致的增殖和传代，而药物筛选和反应预测将受益于更短、更精确的测定以及清晰的决策工具。

 结论

本综述试图概述利用类器官平台进行药物发现和临床应用仍然面临的最重要的挑战。其中一些挑战可以通过正在研究的新方法来克服，例如 3D 生物打印系统、微流体系统、光学代谢成像和液体处理机器人。我们还提出了一个优化的类器官工作流程，其灵感来自于我们提出的所有技术解决方案。