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患者来源异种移植物和患者来源类器官在胰腺癌新治疗方案探索中的应用。综述。

The use of patient-derived xenografts and patient-derived organoids in the search for new therapeutic regimens for pancreatic carcinoma. A review.

作者信息

Gayibov Emin, Sychra Tomáš, Spálenková Alžběta, Souček Pavel, Oliverius Martin

机构信息

3rd Faculty of Medicine, Charles University, Prague, Czech Republic.

3rd Faculty of Medicine, Charles University, Prague, Czech Republic; Centre of Toxicology and Health Safety, National Institute of Public Health, Prague, Czech Republic; Department of General Surgery, 3rd Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czech Republic.

出版信息

Biomed Pharmacother. 2025 Jan;182:117750. doi: 10.1016/j.biopha.2024.117750. Epub 2024 Dec 16.

Abstract

Patient-derived organoids (PDOs) and xenografts (PDXs) are powerful tools for personalized medicine in pancreatic cancer (PC) research. This study explores the complementary strengths of PDOs and PDXs in terms of practicality, genetic fidelity, cost, and labor considerations. Among other models like 2D cell cultures, spheroids, cancer-on-chip systems, cell line-derived xenografts (CDX), and genetically engineered mouse models (GEMMs), PDOs and PDXs uniquely balance genetic fidelity and personalized medicine potential, offering distinct advantages over the simplicity of 2D cultures and the advanced, but often resource-intensive, GEMMs and cancer-on-chip systems. PDOs excel in high-throughput drug screening due to their ease of use, lower cost, and shorter experimental timelines. However, they lack a complete tumor microenvironment. Conversely, PDXs offer a more complex microenvironment that closely reflects patient tumors, potentially leading to more clinically relevant results. Despite limitations in size, number of specimens, and engraftment success, PDXs demonstrate significant concordance with patient responses to treatment, highlighting their value in personalized medicine. Both models exhibit significant genetic fidelity, making them suitable for drug sensitivity testing. The choice between PDOs and PDXs depends on the research focus, resource availability, and desired level of microenvironment complexity. PDOs are advantageous for high-throughput screening of a diverse array of potential therapeutic agents due to their relative ease of culture and scalability. PDXs, on the other hand, offer a more physiologically relevant model, allowing for a comprehensive evaluation of drug efficacy and mechanisms of action.

摘要

患者来源的类器官(PDOs)和异种移植瘤(PDXs)是胰腺癌(PC)研究中用于个性化医疗的强大工具。本研究从实用性、基因保真度、成本和人力因素等方面探讨了PDOs和PDXs的互补优势。在二维细胞培养、球体、芯片上的癌症系统、细胞系来源的异种移植瘤(CDX)和基因工程小鼠模型(GEMMs)等其他模型中,PDOs和PDXs独特地平衡了基因保真度和个性化医疗潜力,与二维培养的简单性以及先进但通常资源密集的GEMMs和芯片上的癌症系统相比具有明显优势。PDOs因其易用性、低成本和较短的实验周期而在高通量药物筛选方面表现出色。然而,它们缺乏完整的肿瘤微环境。相反,PDXs提供了更复杂的微环境,能更紧密地反映患者肿瘤情况,可能产生更具临床相关性的结果。尽管在大小、标本数量和移植成功率方面存在局限性,但PDXs与患者的治疗反应显示出显著的一致性,突出了它们在个性化医疗中的价值。这两种模型都表现出显著的基因保真度,使其适用于药物敏感性测试。在PDOs和PDXs之间的选择取决于研究重点、资源可用性以及所需的微环境复杂程度。由于其相对容易培养和可扩展性,PDOs对于高通量筛选各种潜在治疗药物具有优势。另一方面,PDXs提供了一个更具生理相关性的模型,能够全面评估药物疗效和作用机制。

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