Data Sheet 1_Applications of 3D models in cholangiocarcinoma.pdf

The prognosis for patients diagnosed with cholangiocarcinoma (CCA) is dismal, with an overall 5-year-mortality rate of 80%. Therapeutic approaches for this cancer are very limited and the only curative treatment is total surgical resection despite recent advancements in CCA research. However, only a minority of patients are eligible for surgery due to late-stage diagnosis. Therefore, there is an urgent need to gain a deeper understanding of CCA and to discover new treatments, which can be achieved by utilization and optimization of 3D tumor models. Traditional 2D cell culture is still undeniably important in cancer research, especially for the discovery of biomarkers and drug screening. However, classical 2D tumor models do not represent the tumor biology in its full complexity as they lack the vital interactions between cancer cells, angiogenesis, and tumor microenvironment. In recent years, 3D models, including spheroids, 3D co-culture systems, organoids, tumors-on-a-chip, and the in vivo chorioallantoic membrane (CAM) model, have been used for CCA research. These models enable the study of the tumor microenvironment, investigation of metastases, drug development and testing, cholangiocarcinogenesis and personalized therapy. This review summarizes the applications of the different 3D tumor models that have been used for the investigation of CCA. Moreover, the advantages and disadvantages of the different 3D tumor models are discussed, and suggestions for future research possibilities are described. By optimizing 3D models, the gap between basic research findings and clinical applications can be bridged, enabling the discovery of more effective therapies for CCA and other cancers.

胆管癌（cholangiocarcinoma, CCA）患者的预后极差，总体5年死亡率高达80%。尽管近年来胆管癌研究取得了一定进展，但该癌症的治疗手段仍极为有限，唯一的根治性治疗方式为根治性手术切除。然而多数患者确诊时已属晚期，仅少数人群符合手术指征。因此，亟需深入解析胆管癌的发病机制并开发新型治疗方案，而这可通过3D肿瘤模型的应用与优化得以实现。传统二维（2D）细胞培养在癌症研究中仍具有不可替代的重要地位，尤其在生物标志物发现与药物筛选领域。但经典2D肿瘤模型无法完整还原肿瘤生物学的复杂全貌，因其缺乏癌细胞、血管生成与肿瘤微环境之间的关键相互作用。近年来，包括细胞球体、三维（3D）共培养系统、类器官、器官芯片以及体内绒毛膜尿囊膜（chorioallantoic membrane, CAM）模型在内的多种3D模型已被应用于胆管癌研究。此类模型可支持肿瘤微环境解析、转移机制探究、药物开发与测试、胆管癌发生过程分析以及个性化治疗等研究方向。本综述总结了当前用于胆管癌研究的各类3D肿瘤模型的应用场景，同时讨论了不同3D肿瘤模型的优缺点，并对未来的研究方向提出了建议。通过优化3D模型，可弥合基础研究成果与临床应用之间的鸿沟，助力开发针对胆管癌及其他癌症的更有效治疗方案。