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[患者来源肿瘤异种移植模型在肿瘤转化医学中的应用与发展]

[Application and development of patient-derived tumor xenograft model in translational medicine of tumor].

作者信息

Wang Zhenqiang, Zhu Zhenggang

机构信息

Department of Digestive Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2017 May 25;20(5):596-600.

Abstract

Development of novel drugs is an integral part of the translational medicine in the field of cancer research, and the construction and application of preclinical animal models play vital roles in drugs development. Patient-derived tumor xenograft models (PDX) have been shown to be more accurate in prediction of clinical outcomes of novel drugs and are being used for preclinical drug evaluation based on the fact that PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor. To set up PDX model, primary or metastatic tumor are achieved to translate into immune-deficiency mice. The tumor in immune-deficiency mouse is acquired to translate to other immune-deficiency mouse to generate stable PDX model, which usually is affected by the strain of mouse, translation method and translation location in mouse. PDX models recapitulate the same histology and gene expression as the original patients' carcinoma. PDX models can accurately predict the effectiveness of novel drugs, screen more predictive biomarker for drug resistance and optimize the use of classic drugs in clinic. However, sole source of surgical resection of tumor, long time of construction, high failure rate and hardly used in evaluating immune drugs would be the barriers to be overcome to improve PDX models. The methodological issues, salient features, practical applications, and future directions of PDX models will be illustrated.

摘要

新型药物的研发是癌症研究领域转化医学的一个重要组成部分,临床前动物模型的构建和应用在药物研发中发挥着至关重要的作用。患者来源的肿瘤异种移植模型(PDX)已被证明在预测新型药物的临床疗效方面更为准确,并且基于PDX模型大多保留其供体肿瘤的主要组织学和遗传学特征这一事实,正被用于临床前药物评估。为了建立PDX模型,获取原发性或转移性肿瘤并移植到免疫缺陷小鼠体内。从免疫缺陷小鼠体内获取肿瘤并移植到其他免疫缺陷小鼠体内以生成稳定的PDX模型,这通常受到小鼠品系、移植方法和小鼠体内移植位置的影响。PDX模型重现了与原始患者癌相同的组织学和基因表达。PDX模型可以准确预测新型药物的有效性,筛选出更具预测性的耐药生物标志物,并优化经典药物在临床上的使用。然而,肿瘤手术切除的单一来源、构建时间长、失败率高以及难以用于评估免疫药物将是改进PDX模型需要克服的障碍。本文将阐述PDX模型的方法学问题、显著特征、实际应用及未来发展方向。

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