We discuss the importance of the in vivo models in elucidating cancer biology, focusing on the patient-derived xenograft (PDX) models, which are classic and standard functional in vivo platforms for preclinical evaluation. We provide an overview of the most representative models, including cell-derived xenografts (CDX), tumor and metastatic cell-derived xenografts, and PDX models utilizing humanized mice (HM). The orthotopic models, which could reproduce the cancer environment and its progression, similar to human tumors, are particularly common. The standard procedures and rationales of gastric adenocarcinoma (GAC) orthotopic models are addressed. Despite the significant advantages of the PDX models, such as recapitulating key features of human tumors and enabling drug testing in the in vivo context, some challenges must be acknowledged, including loss of heterogeneity, selection bias, clonal evolution, stroma replacement, tumor micro-environment (TME) changes, host cell carryover and contaminations, human-to-host cell oncogenic transformation, human and host viral infections, as well as limitations for immunologic research. To compensate for these limitations, other mouse models, such as syngeneic and humanized mouse models, are currently utilized. Overall, the PDX models represent a powerful tool in cancer research, providing critical insights into tumor biology and potential therapeutic targets, but their limitations and challenges must be carefully considered for their effective use. Lastly, we present an intronic quantitative PCR (qPCR) method to authenticate, detect, and quantify human/murine cells in cell lines and PDX samples.
本文探讨了体内模型在阐明癌症生物学中的重要性，重点聚焦于患者来源异种移植（PDX）模型，该模型是临床前评估中经典且标准的功能性体内平台。我们对最具代表性的模型进行了概述，包括细胞来源异种移植（CDX）、肿瘤及转移细胞来源异种移植，以及利用人源化小鼠（HM）的PDX模型。其中，能够模拟人类肿瘤的癌症环境及其进展的原位移植模型尤为常见。本文详细阐述了胃腺癌（GAC）原位移植模型的标准操作流程及其理论基础。尽管PDX模型具有显著优势，如重现人类肿瘤的关键特征并在体内环境中进行药物测试，但也必须承认其面临的一些挑战，包括异质性丧失、选择偏倚、克隆演化、基质替代、肿瘤微环境（TME）变化、宿主细胞残留与污染、人源至宿主细胞的致癌转化、人源与宿主病毒感染，以及在免疫学研究中的局限性。为弥补这些不足，目前正在使用其他小鼠模型，如同源移植和人源化小鼠模型。总体而言，PDX模型是癌症研究中的有力工具，为肿瘤生物学和潜在治疗靶点提供了关键见解，但在有效利用时，必须仔细考虑其局限性和挑战。最后，我们提出了一种内含子定量PCR（qPCR）方法，用于鉴定、检测和定量细胞系及PDX样本中的人源/鼠源细胞。
Challenges and Prospects of Patient-Derived Xenografts for Cancer Research
肿瘤(癌症)患者之家