Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Med Res Rev. 2023 Jan;43(1):212-236. doi: 10.1002/med.21924. Epub 2022 Aug 27.
The cost of antitumor drug development is enormous, yet the clinical outcomes are less than satisfactory. Therefore, it is of great importance to develop effective drug screening methods that enable accurate, rapid, and high-throughput discovery of lead compounds in the process of preclinical antitumor drug research. An effective solution is to use the patient-derived xenograft (PDX) tumor animal models, which are applicable for the elucidation of tumor pathogenesis and the preclinical testing of novel antitumor compounds. As a promising screening model organism, zebrafish has been widely applied in the construction of the PDX tumor model and the discovery of antineoplastic agents. Herein, we systematically survey the recent cutting-edge advances in zebrafish PDX models (zPDX) for studies of pathogenesis mechanisms and drug screening. In addition, the techniques used in the construction of zPDX are summarized. The advantages and limitations of the zPDX are also discussed in detail. Finally, the prospects of zPDX in drug discovery, translational medicine, and clinical precision medicine treatment are well presented.
抗肿瘤药物研发成本巨大，但临床疗效却不尽如人意。因此，开发有效的药物筛选方法对于在抗肿瘤药物临床前研究过程中准确、快速、高通量地发现先导化合物非常重要。一种有效的解决方案是使用患者来源的异种移植（PDX）肿瘤动物模型，该模型适用于阐明肿瘤发病机制和新型抗肿瘤化合物的临床前测试。斑马鱼作为一种很有前途的筛选模型生物，已广泛应用于 PDX 肿瘤模型的构建和抗肿瘤药物的发现。在此，我们系统地综述了斑马鱼 PDX 模型（zPDX）在发病机制研究和药物筛选方面的最新前沿进展。此外，还总结了构建 zPDX 所使用的技术。详细讨论了 zPDX 的优缺点。最后，还很好地展示了 zPDX 在药物发现、转化医学和临床精准医学治疗方面的前景。
