Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. An unmet need exists for reliable biomarkers and in vitro models capable of predicting patient drug response to advance personalized medicine. Traditional models fail to represent the tumor’s complexity and the role of the stromal environment in chemoresistance. Patient-derived organoids (PDOs) overcome these limitations, enabling multi-omics profiling and reliable drug testing for functional precision medicine. This review provides a comprehensive overview of PDAC PDO research, emphasizing the following major areas: (i) the genetic and phenotypic fidelity of PDOs, (ii) their predictive value for drug response and chemoresistance, (iii) the integration of the extracellular matrix and tumor microenvironment (TME) components, and (iv) emerging technologies. Studies confirm that PDOs faithfully represent the primary tumor’s specific genetic features and retain intratumoral heterogeneity. PDO-based platforms have demonstrated a strong correlation between in vitro drug sensitivity and in vivo efficacy in xenograft models, validating their utility for identifying drug candidates, repurposing existing drugs, and determining effective combinations. Efforts are ongoing to integrate crucial TME components, like cancer-associated fibroblasts, using innovative co-culture platforms such as fused PDOs and InterOMaX, to better model desmoplasia and chemoresistance mechanisms. Furthermore, PDO technology is converging with microphysiological systems and artificial intelligence tools to facilitate high-throughput drug screening and dynamic, real-time monitoring of therapeutic effects. The integration of PDOs into biobanks and advanced screening platforms holds the potential to accelerate drug discovery and improve therapeutic outcomes for PDAC patients, if challenges related to protocol standardization and regulatory acceptance are addressed.
胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一。目前亟需可靠的生物标志物和能够预测患者药物反应的体外模型，以推动个体化医疗的发展。传统模型无法充分体现肿瘤的复杂性及基质微环境在化疗耐药中的作用。患者来源类器官（PDOs）克服了这些局限，能够通过多组学分析和可靠的药物测试实现功能性精准医疗。本综述全面概述了PDAC PDOs的研究进展，重点聚焦以下核心领域：（一）PDOs的遗传与表型保真度；（二）其对药物反应和化疗耐药的预测价值；（三）细胞外基质与肿瘤微环境（TME）组分的整合；（四）新兴技术应用。研究证实，PDOs能准确反映原发肿瘤的特异性遗传特征，并保留肿瘤内异质性。基于PDOs的平台已在异种移植模型中证明体外药物敏感性与体内疗效具有强相关性，验证了其在候选药物筛选、现有药物再利用及有效联合方案确定方面的应用价值。当前研究正通过融合PDOs、InterOMaX等创新共培养平台，持续整合癌症相关成纤维细胞等关键TME组分，以更好地模拟纤维增生及化疗耐药机制。此外，PDOs技术正与微生理系统和人工智能工具相结合，以促进高通量药物筛选及治疗效果的动态实时监测。若能解决方案标准化和监管认可方面的挑战，将PDOs整合至生物样本库和先进筛选平台，将有望加速药物研发进程并改善PDAC患者的治疗效果。
Pancreatic Cancer Organoids: Modeling Disease and Guiding Therapy
肿瘤(癌症)患者之家