Department of Clinical Medicine, Shantou University Medical College, Shantou, China.
College of Life Sciences, Hubei Normal University, Huangshi, China.
Animal Model Exp Med. 2023 Oct;6(5):381-398. doi: 10.1002/ame2.12349. Epub 2023 Sep 7.
Patient-derived tumor xenograft (PDX) models, a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice, have emerged as a pivotal approach in translational research, particularly in advancing precision medicine. As the first stage of PDX development, the patient-derived orthotopic xenograft (PDOX) models implant tumor tissue in mice in the corresponding anatomical locations of the patient. The PDOX models have several advantages, including high fidelity to the original tumor, heightened drug sensitivity, and an elevated rate of successful transplantation. However, the PDOX models present significant challenges, requiring advanced surgical techniques and resource-intensive imaging technologies, which limit its application. And then, the humanized mouse models, as well as the zebrafish models, were developed. Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay. The humanized mouse models are a hot topic in PDX model research. Regarding zebrafish patient-derived tumor xenografts (zPDX) and patient-derived organoids (PDO) as promising models for studying cancer and drug discovery, zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time. PDO models provide a cost-effective approach for drug testing that replicates the in vivo environment and preserves important tumor-related information for patients. The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.
患者来源肿瘤异种移植(PDX)模型,一种涉及从癌症患者手术提取肿瘤组织并随后移植到免疫缺陷小鼠中的方法,已成为转化研究的关键方法,特别是在推进精准医学方面。作为 PDX 发展的第一阶段,患者来源的原位异种移植(PDOX)模型将肿瘤组织植入患者相应解剖位置的小鼠中。PDOX 模型具有几个优点,包括与原始肿瘤高度相似、提高药物敏感性和更高的移植成功率。然而,PDOX 模型也存在重大挑战,需要先进的手术技术和资源密集型成像技术,这限制了其应用。然后,开发了人源化小鼠模型和斑马鱼模型。人源化小鼠模型包含类似于肿瘤和免疫系统相互作用的人类免疫环境。人源化小鼠模型是 PDX 模型研究的热门话题。关于作为研究癌症和药物发现有前途模型的斑马鱼患者来源肿瘤异种移植(zPDX)和患者来源类器官(PDO),zPDX 模型用于将肿瘤移植到斑马鱼中,作为一种新的个性化医学动物模型,具有减少患者等待时间的优势。PDO 模型提供了一种具有成本效益的药物测试方法,复制了体内环境并保留了患者重要的肿瘤相关信息。本综述强调了 PDX 每个新阶段的功能特征,并探讨了这个快速发展领域的挑战和前瞻性发展。