摘要
随着肿瘤发病率的持续上升,肿瘤新药的研发愈加迫切。有效的临床前模型对肿瘤新药的安全性和有效性评估至关重要。本文综述了目前常用的临床前评价模型,包括患者来源细胞系、患者来源类器官、细胞系来源异种移植物、患者来源异种移植物、人源化免疫系统小鼠以及基因工程化小鼠。患者来源细胞系是最基础的模型,广泛用于药物筛选和机制研究;类器官模型则通过三维结构更好地模拟肿瘤微环境;患者来源异种移植物在个性化治疗研究中发挥着重要作用;人源化免疫系统小鼠是免疫疗法研究的重要工具;而基因工程化小鼠通过精确的基因操作,模拟人类肿瘤的发生与发展。本文分析了这些模型的优势与局限性,展望了技术进步对临床前评价模型的影响。
With the continuous rise in cancer incidence,the development of new cancer drugs has become increasingly important.Effective preclinical evaluation models are essential for assessing the safety and efficacy of new drugs.This article reviews several commonly used preclinical evaluation models,including patient-derived cell lines(PDCs),patient-derived organoids(PDOs),cell line-derived xenografts(CDX),patient-derived xenografts(PDX),humanized immune system mice,and genetically engineered mice(GEMMs).Patient-derived cell lines are fundamental models widely used for drug screening and mechanism research.Organoid models,with their three-dimensional structure,better simulate the tumor microenvironment.PDX models play an important role in personalized treatment research.Humanized immune system mice are crucial tools in immunotherapy studies,while genetically engineered mice,through precise genetic modifications,simulate the occurrence and progression of human tumors.This article evaluates the strengths and weaknesses of these models and explores how technological advancements influence preclinical evaluation.
作者
张伟
王晨
江涛
Wei Zhang;Chen Wang;Tao Jiang(Beijing Tiantan Hospital,Capital Medical University,Beijing 100190,China;Glioma Clinical Diagnosis and Research Center,Capital Medical University,Beijing 100190,China;Beijing Institute for Brain Disorders,Institute of Brain Tumor Research,Beijing 100190,China;China National Clinical Research Center for Neurological Diseases,Beijing 100070,China)
出处
《中国科学基金》
北大核心
2025年第1期111-121,共11页
Bulletin of National Natural Science Foundation of China
基金
国家自然科学基金项目(82072768,81201993)
青年北京学者项目(No.055)
北京高校卓越青年科学家计划项目(JWZQ20240101026)的资助。
关键词
肿瘤新药
临床前模型
类器官
荷瘤小鼠
异种移植物
人源化免疫系统小鼠
novel anticancer drugs
preclinical models
organoids
tumor-bearing mice
patient-derived xenografts
humanized immune system mice
