新的临床前研究小鼠模型：肿瘤患者来源的移植瘤 - tumor.pdfVIP

肿瘤2014 年3 月第34 卷第3 期　TUM OR Vol. 34, March 2014　　 291 DOI: 10.3781/j .issn.1000-7431.2014.03.016 Copyright© 2014 by TUM OR Review 综述 · 新的临床前研究小鼠模型：肿瘤患者来源的移植瘤 张峻岭，陈子逸，陈国卫，刘玉村 北京大学第一医院普通外科，北京　100034 [摘要]　在以往研究中，由裸鼠和肿瘤细胞系来源的皮下移植瘤组成的小鼠模型为研究新的癌症治疗策略提供了 一个临床前测试系统。但是这种传统模型缺乏肿瘤异质性和 自发性远隔转移的能力，很难准确模拟临床患者的真 实病情。近年来，研究者开发出一种更好的临床前模型，即在小鼠体内形成肿瘤患者来源的移植瘤 （patient-derived xenografts ，PDXs ）。研究表明，将各种患者来源的肿瘤组织移植到免疫缺陷或转基因小鼠的恰当部位可以更准确 地模拟患者的原发肿瘤，尤其是其远隔转移能力。由于 PDXs 不仅忠实地保留了患者肿瘤的分子表型和基因型变 化，而且能够再现原发肿瘤的异质性，因此可被应用于肿瘤耐药机制的研究。本综述总结了建立 PDXs 模型的方法， 检验患者肿瘤和小鼠移植瘤相似性的方法，以及这种模型在新药研发中的优点和局限性。 [关键词]　肿瘤，实验性；疾病模型，动物；异种移植模型抗肿瘤试验；小鼠，裸；患者来源的移植瘤 [中图分类号]　R73-352 [文献标志码] A [文章编号]　1000-7431 (2014) 03-0291-04 New preclinical mouse model: patient-derived xenografts ZHANG Jun-ling, CHEN Zi-yi, CHEN Guo-wei, LIU Yu-cun Department of General Surgery, Peking University First Hospital, Beijing 100034, China [A BSTRACT]　The mouse models of nude mice bearing subcutaneous xenografts derived from tumor cell lines provide a preclinical testing system for exploring novel anticancer therapies. However, due to the lack of heterogeneity and an ability of spontaneous distant metastasis, these traditional models are difficult to accurately simulate the clinical condition of the patient. Recently, some researchers have developed better preclinical models by using patient-derived xenografts (PDXs) in mice. It has been shown that transplanting a variety of patient-derived tumor tissues into an appropriate anatomical site of immunocompromised or transgenic mice can authentically mimic the primary tumor in patients, especially with distant metastatic ability. PDXs can not only faithfully preserve the molecular phenotypes and genomic alterations of the pri