Montagner Agata, Lemberger-Viehmann Laura, Reitberger Nadine, Schmidt Milena, Scheruebl Julia, Pion Eric, Wagner Benedikt J, Pilarsky Christian, Grützmann Robert, Aung Thiha, Hackl Christina, Haerteis Silke
Institute for Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany.
Faculty of Applied Healthcare Science, Deggendorf Institute of Technology, Deggendorf, Germany.
Front Oncol. 2025 Jul 31;15:1598552. doi: 10.3389/fonc.2025.1598552. eCollection 2025.
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 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.
被诊断为胆管癌(CCA)的患者预后很差,总体5年死亡率为80%。尽管CCA研究最近取得了进展,但这种癌症的治疗方法非常有限,唯一的根治性治疗是完全手术切除。然而,由于诊断较晚,只有少数患者适合手术。因此,迫切需要更深入地了解CCA并发现新的治疗方法,这可以通过利用和优化3D肿瘤模型来实现。传统的二维细胞培养在癌症研究中仍然不可否认地很重要,特别是在生物标志物的发现和药物筛选方面。然而,经典的二维肿瘤模型无法完全呈现肿瘤生物学的复杂性,因为它们缺乏癌细胞、血管生成和肿瘤微环境之间至关重要的相互作用。近年来,三维模型,包括球体、三维共培养系统、类器官、芯片上的肿瘤以及绒毛尿囊膜(CAM)模型,已被用于CCA研究。这些模型能够用于研究肿瘤微环境、转移、药物开发和测试、胆管癌发生以及个性化治疗。这篇综述总结了已用于CCA研究的不同三维肿瘤模型的应用。此外,还讨论了不同三维肿瘤模型的优缺点,并描述了未来研究可能性的建议。通过优化三维模型,可以弥合基础研究结果与临床应用之间的差距,从而为CCA和其他癌症发现更有效的治疗方法。
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