胆管癌动物模型研究进展与思考  

Research on animal models of cholangiocarcinoma

作　　者：周星言 张迪[1] 姚楠[1] 洪健 Zhou Xingyan;Zhang Di;Yao Nan;Hong Jian(Department of Pathophysiology,School of Medicine and Public Health,Jinan University,Guangzhou 510630,China)

机构地区：[1]暨南大学基础医学与公共卫生学院病理生理学系,广州510630

出　　处：《中华实验外科杂志》2023年第4期803-808,共6页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(81871987、82172602);中央高校基本科研业务费专项资金资助(21620106)。

摘　　要：胆管癌(CCA)是起源于胆道上皮的恶性肿瘤,起病隐匿,侵袭性强,治疗手段有限,预后差。胆管癌动物模型在肿瘤发生发展机制的研究及抗肿瘤药物评价体系中发挥重要作用,主要分为诱发模型及移植模型。诱发动物模型包括化学致癌物诱发模型、胆汁淤积模型、转基因模型及基因转导模型等,移植动物模型包括人源胆管癌(细胞/组织)异种移植模型、同系肿瘤移植模型、胆管类器官移植模型等。其中,转基因模型在胆管癌发生发展机制与信号通路的研究中具有独特的优势,常被应用于靶向药物的筛选研发及药效评估;人源胆管癌组织异种移植(PDX)模型为临床前药物测试及个体化药物筛选提供了较为理想的平台,在精准医疗中发挥着重要作用。本文结合国内外现有的胆管癌动物模型,对其优缺点、应用现状及发展趋势作如下综述。Cholangiocarcinoma(CCA)is a devastating malignancy associated with poor outcomes due to late diagnosis and limited therapeutic options.Preclinical in vivo models of CCA have become increasingly paramount as they are helpful not only for the study of the fundamental molecular mechanisms of CCA but also for developing novel and effective therapeutic approaches of this fatal cancer.Various CCA animal models exist including carcinogen-based models in which animals develop CCA after exposure to carcinogens such as chemicals,cholestasis,and genetic mutation,as well as xenograft tumors derived from xenotransplantation of CCA cells,organoids,and patient-derived xenograft(PDX).Notably,among these models,genetic models can be used to explore the causes and molecular mechanisms of cholangiocarcinogenesis,progression,and metastasis at the level of specific genes,to identify biomarkers for prognosis,and to preclinically assess the therapeutic response to targeted drugs.PDX models may be a promising platform for individualized anticancer drug screening,discovery of drug-resistance biomarker and prediction of individual response to anticancer treatment.We are intended to help investigators understand the strengths,weaknesses,application status and the potential of the currently used animal models of human CCA,aiding in the selection of the one that is the best for their research needs.

关 键 词：胆管癌 动物模型 

分 类 号：R735.8[医药卫生—肿瘤] R-332[医药卫生—临床医学]