人源肿瘤异种移植模型的构建与应用研究进展  

Advance in establishment and application of patient-derived tumor xenograft model

作　　者：叶润泽 王超[1] 秦超 杨兆红 林志[1] 屈哲[1] 李双星 杨艳伟[1] 张頔[1] 杨勇 王三龙[1] 霍桂桃[1] YE Runze;WANG Chao;QIN Chao;YANG Zhaohong;LIN Zhi;QU Zhe;LI Shuangxing;YANG Yanwei;ZHANG Di;YANG Yong;WANG Sanlong;HUO Guitao(Key Laboratory of Beijing for Safety Evaluation of Drugs,National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Beijing 100176,China;School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心,药物非临床安全评价研究北京市重点实验室,北京100176 [2]中国药科大学基础医学与临床药学学院,江苏南京211198

出　　处：《药物评价研究》2024年第10期2420-2426,共7页Drug Evaluation Research

基　　金：中国食品药品检定研究院关键技术研究基金项目(GJJS-2022-6-5)。

摘　　要：人源肿瘤异种移植(PDX)模型是一种将人源肿瘤组织或患者来源的原代细胞植入免疫缺陷鼠体内,经传代培养后形成的体内肿瘤模型。这一模型来源于临床患者,且能与鼠体内微环境互相作用,作为动物模型可以较大程度地还原人类肿瘤的特征,因而其在临床前抗肿瘤药物的药效学评价、个性化治疗,以及肿瘤分布及转移机制研究等方面广受青睐。PDX模型构建成功与否与肿瘤的恶性程度、肿瘤组织的新鲜程度、以及小鼠的免疫缺陷程度均有较大的关联性。全球每年只有极少数抗癌新药通过监管部门审批,其原因是缺乏规范的临床前药效学研究模型和评价技术体系,进而导致抗肿瘤药物的研发进程被严重限制。因此,构建合理、可靠的临床前抗肿瘤药物的药效学评价模型和建立科学的评价技术体系势在必行。为更好地了解PDX模型,从PDX模型的构建方法和实际应用进行综述,以期为我国临床前抗肿瘤药物药效学评价的有效新模型构建及应用提供参考信息。Patient-derived tumor xenograft(PDX)model is an in vivo tumor model implanting human tumor tissues or patient-derived primary cells into immunodeficient mice,and then culturing the cells in passaging.PDX model is derived from clinical patients and can interact with microenvironment in mice.As an animal model,PDX model can largely restore the characteristics of human tumors,thus it is widely used in preclinical pharmacodynamic evaluation of anti-tumor drugs,personalized medical treatment,as well as research on the distribution and metastatic mechanism of tumors,etc.The success of PDX model establishment is highly correlated with tumors'malignancy and freshness,as well as immunodeficiency in mice.It's a fact that only few new anti-cancer drugs are approved by the regulatory authorities each year.Due to the lack of standardized preclinical evaluation models and system,the research and development process of antitumor drugs in China has been seriously limited,thus it is imperative to establish reasonable and reliable preclinical efficacy evaluation models and a scientific evaluation technology system for anti-tumor drugs.This paper will review the establishment and application of PDX model,with a view to providing reference for establishing and applicating effective new models for the preclinical evaluation of anti-tumor drugs in China.

关 键 词：人源肿瘤异种移植模型 抗肿瘤药物 药效学评价 个性化治疗 肿瘤转移机制 

分 类 号：R965.1[医药卫生—药理学]