胰腺导管腺癌（PDAC）是一种侵袭性癌症，预后不良，全球死亡率不断上升。由于缺乏早期症状和生物标志物，诊断较晚，治疗主要局限于化疗，而化疗很快就会遇到耐药性。 PDAC 治疗创新因其复杂且异质的耐药性而受到阻碍，包括关键基因的突变和富含基质的免疫抑制肿瘤微环境。最近对 PDAC 耐药性的研究强调需要合适的体外和离体模型来复制其复杂的分子和微环境景观。这篇综述总结了这些模型的进展，这些模型可以帮助对抗化疗耐药性并作为发现新疗法的平台。永生化细胞系具有同质性、无限增殖和可重复性，但尽管存在许多对吉西他滨耐药的 PDAC 细胞系，但可用于对其他药物耐药的模型较少。来自 PDAC 患者的类器官在模拟肿瘤异质性和化疗敏感性方面显示出前景。正在开发包含基质细胞和免疫细胞的生物反应器、共培养系统和器官切片，以了解肿瘤-基质相互作用以及肿瘤微环境在耐药性中的作用。最后，另一种创新方法是三维生物打印，它可以创建类似于 PDAC 架构的组织样结构，从而可以进行药物筛选。这些先进的模型可以指导研究人员选择最佳的体外测试，从而有可能改善治疗策略和患者结果。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis and rising global deaths. Late diagnosis, due to absent early symptoms and biomarkers, limits treatment mainly to chemotherapy, which soon encounters resistance. PDAC treatment innovation is hampered by its complex and heterogeneous resistant nature, including mutations in key genes and a stromal-rich, immunosuppressive tumour microenvironment. Recent studies on PDAC resistance stress the need for suitable in vitro and ex vivo models to replicate its complex molecular and microenvironmental landscape. This review summarises advances in these models, which can aid in combating chemoresistance and serve as platforms for discovering new therapeutics. Immortalised cell lines offer homogeneity, unlimited proliferation, and reproducibility, but while many gemcitabine-resistant PDAC cell lines exist, fewer models are available for resistance to other drugs. Organoids from PDAC patients show promise in mimicking tumour heterogeneity and chemosensitivity. Bioreactors, co-culture systems and organotypic slices, incorporating stromal and immune cells, are being developed to understand tumour-stroma interactions and the tumour microenvironment's role in drug resistance. Lastly, another innovative approach is three-dimensional bioprinting, which creates tissue-like structures resembling PDAC architecture, allowing for drug screening. These advanced models can guide researchers in selecting optimal in vitro tests, potentially improving therapeutic strategies and patient outcomes.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.