Australian Prostate Cancer Research Centre - Queensland, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Translational Research Institute, Brisbane, QLD, Australia.
Methods Mol Biol. 2024;2806:153-185. doi: 10.1007/978-1-0716-3858-3_12.
Patient-derived xenografts (PDXs) are a valuable preclinical research platform generated through transplantation of a patient's resected tumor into an immunodeficient or humanized mouse. PDXs serve as a high-fidelity avatar for both precision medicine and therapeutic testing against the cancer patient's disease state. While PDXs show mixed response to initial establishment, those that successfully engraft and can be sustained with serial passaging form a useful tool for basic and translational prostate cancer (PCa) research. While genetically engineered mouse (GEM) models and human cancer cell lines, and their xenografts, each play beneficial roles in discovery science and initial drug screening, PDX tumors are emerging as the gold standard approach for therapeutic proof-of-concept prior to entering clinical trial. PDXs are a powerful platform, with PCa PDXs shown to represent the original patient tumor cell population and architecture, histopathology, genomic and transcriptomic landscape, and heterogeneity. Furthermore, PDX response to anticancer drugs in mice has been closely correlated to the original patient's susceptibility to these treatments in the clinic. Several PDXs have been established and have undergone critical in-depth characterization at the cellular and molecular level across multiple PCa tumor subtypes representing both primary and metastatic patient tumors and their inherent levels of androgen responsiveness and/or treatment resistance, including androgen-sensitive, castration resistant, and neuroendocrine PCa. Multiple PDX networks and repositories have been generated for the collaborative and shared use of these vital translational cancer tools. Here we describe the creation of a PDX maintenance colony from an established well-characterized PDX, best practice for PDX maintenance in mice, and their subsequent application in preclinical drug testing. This chapter aims to serve as a go to resource for the preparation and adoption of PCa PDX models in the research laboratory and for their use as a valuable preclinical platform for translational research and therapeutic agent development.
患者来源异种移植（PDX）是一种通过将患者切除的肿瘤移植到免疫缺陷或人源化小鼠中而产生的有价值的临床前研究平台。PDX 作为精准医学和针对癌症患者疾病状态的治疗测试的高保真模拟物。虽然 PDX 对初始建立的反应不一，但那些成功植入并可通过连续传代维持的 PDX 形成了基础和转化前列腺癌（PCa）研究的有用工具。虽然基因工程小鼠（GEM）模型和人癌细胞系及其异种移植在发现科学和初步药物筛选中都发挥了有益作用，但 PDX 肿瘤正在成为进入临床试验前治疗概念验证的黄金标准方法。PDX 是一个强大的平台，PCa PDX 被证明代表了原始患者肿瘤细胞群体和结构、组织病理学、基因组和转录组景观以及异质性。此外，PDX 对小鼠中抗癌药物的反应与原始患者对这些治疗在临床上的敏感性密切相关。已经建立了几个 PDX，并在多个 PCa 肿瘤亚型中进行了关键的细胞和分子水平的深入表征，这些亚型代表了原发性和转移性患者肿瘤及其内在的雄激素反应性和/或治疗抵抗性，包括雄激素敏感性、去势抵抗性和神经内分泌性 PCa。已经生成了多个 PDX 网络和存储库，用于这些重要的转化癌症工具的协作和共享使用。在这里，我们描述了从一个已建立的经过充分表征的 PDX 中创建 PDX 维持群体的过程、在小鼠中维持 PDX 的最佳实践，以及它们随后在临床前药物测试中的应用。本章旨在为研究实验室中 PCa PDX 模型的制备和采用以及作为转化研究和治疗剂开发有价值的临床前平台提供参考。
