药物评价研究2024,Vol.47Issue(10) :2420-2426.DOI:10.7501/j.issn.1674-6376.2024.10.023

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

叶润泽 王超 秦超 杨兆红 林志 屈哲 李双星 杨艳伟 张頔 杨勇 王三龙 霍桂桃
药物评价研究2024,Vol.47Issue(10) :2420-2426.DOI:10.7501/j.issn.1674-6376.2024.10.023

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

叶润泽 1王超 2秦超 2杨兆红 1林志 2屈哲 2李双星 2杨艳伟 2张頔 2杨勇 3王三龙 2霍桂桃2
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作者信息

  • 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;中国药科大学基础医学与临床药学学院,江苏南京 211198
  • 2. 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
  • 3. 中国药科大学基础医学与临床药学学院,江苏南京 211198
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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.

Abstract

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

Key words

patient-derived tumor xenograft/anti-tumor drug/pharmacodynamic evaluation of drugs/individualized treatment/metastatic mechanism of tumor

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基金项目

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)

出版年

2024
药物评价研究
天津药物研究院 中国药学会

药物评价研究

CSTPCD北大核心
影响因子:1.199
ISSN:1674-6376
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