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中华结直肠疾病电子杂志 ›› 2025, Vol. 14 ›› Issue (01) : 40 -46. doi: 10.3877/cma.j.issn.2095-3224.2025.01.004

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结直肠癌肝转移研究模型的现状及展望
袁佳莹1, 范小彧2,3, 费博1, 喻春钊1,3,()   
  1. 1. 211112 南京医科大学附属逸夫医院普外科
    2. 226300 南通市通州区人民医院普通外科
    3. 210011 南京医科大学第二附属医院普外科
  • 收稿日期:2024-07-24 出版日期:2025-02-25
  • 通信作者: 喻春钊
  • 基金资助:
    国家自然科学基金面上项目(No.82373293)国家重点研发计划(No.2018YFE0127300)江苏省卫生健康委员会研究项目(No.ZD2022063)江苏省“333 工程培养资金”项目(No.BRA2020091)江苏省科技计划重点项目(No.BE2019759)

Current situation and prospect of liver metastasis research model for colorectal cancer

Jiaying Yuan1, Xiaoyu Fan2,3, Bo Fei1, Chunzhao Yu1,3,()   

  1. 1. Department of General Surgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211112, China
    2. Department of General Surgery, Nantong Tongzhou People's Hospital, Nantong 226300, China
    3. Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China
  • Received:2024-07-24 Published:2025-02-25
  • Corresponding author: Chunzhao Yu
引用本文:

袁佳莹, 范小彧, 费博, 喻春钊. 结直肠癌肝转移研究模型的现状及展望[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(01): 40-46.

Jiaying Yuan, Xiaoyu Fan, Bo Fei, Chunzhao Yu. Current situation and prospect of liver metastasis research model for colorectal cancer[J/OL]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2025, 14(01): 40-46.

结直肠癌肝转移(CRLM)是结直肠癌患者最主要的死亡原因之一,其严重威胁着人民群众的生命安全,阻碍了社会经济的繁荣发展。随着我国结直肠癌发病率逐年增加,CRLM 的危害也日益突显。在这样的背景下,如何科学有效的建立CRLM 模型,以促进对肿瘤侵袭转移过程的深入了解,揭示相应机制,评估不同诊疗方案的效果,最终实现CRLM 的早期防诊治应是当前研究的重点和难点。传统的CRLM 模型包括致癌物诱导模型、原位种植模型、异位种植模型、异种移植模型及基因工程小鼠模型。近年来随着科学技术的不断进步,新的造模方法如微流控芯片模型等不断涌现,提供了更多、更新的选择。本文回顾了国内外相关文献,对传统小鼠模型和新兴造模方法进行深入探讨,旨在比较各造模方法的优缺点并介绍最新研究成果,为CRLM 模型的科学建立提供一定指导,最终为CRLM 患者带来更科学的个性化治疗。

Colorectal cancer liver metastasis (CRLM) is the most important cause of death in colorectal cancer patients, which seriously threatens the life safety of people and hinders the prosperity and development of society and economy.With the increasing incidence of colorectal cancer in our country,the harm of CRLM is becoming more and more obvious.In this context, how to establish a scientific and effective CRLM model to promote the in-depth understanding of the tumor invasion and metastasis process,reveal the corresponding mechanism, evaluate the effect of different diagnosis and treatment schemes, and finally realize the early prevention and treatment of CRLM should be the focus and difficulty of current research.Traditional CRLM models include carcinogen induction model, orthotopic model, heterotopic model,xenogenic implantation model and genetically engineered mouse model.In recent years, with the continuous progress of science and technology, new modeling methods such as microfluidic chip model have emerged,providing more updating options.In this paper, relevant literature at home and abroad was reviewed, and the advantages and disadvantages of traditional mouse models and emerging modeling methods were discussed in depth, aiming to compare the advantages and disadvantages of each modeling method and introduce the latest research results, so as to provide certain guidance for the scientific establishment of CRLM model and ultimately bring more scientific personalized treatment for CRLM patients.

表1 各模型优缺点及适用范围
模型类型 优点 缺点 适用范围
CIM 模型 操作简便 稳定性差
耗时,肝转移不同步
饮食对CRLM 的影响
原位种植模型 肿瘤微环境与人类相似
转移的发生是自然过程
肿瘤侵袭转移的进程与人类相似
手术技术难度系数大
稳定性差
耗时,肝转移不同步
肿瘤对药物的反应
CRLM 机制的研究
异位种植模型 皮下: 操作简便
易于观察
脾内等:操作相对简单
肝转移成功率高
实验时间短
稳定性好
皮下: 稳定性差
肿瘤微环境与人类差异大
耗时,肝转移不同步
脾内等: 仅代表肿瘤转移的晚期阶段
快速成模,稳定性好
GEMM 模型 提供肿瘤发生过程中特异性基因突变影响的信息
肿瘤微环境与人类相似
转移的发生是自然过程
耗时,成本高,肝转移率低
特定基因突变可致胚胎致死性、严重发育缺陷或不育
不利于药物疗效的评估
CRLM 患者靶向治疗的研究
PDX 模型 更准确地反映肿瘤的特征和遗传多样性 成本高,肝转移率低
耗时,技术操作难度大
个性化药物治疗
PDOX 模型 保留肿瘤的异质性且具有完整的三维组织结构稳定的遗传特征
减少细胞体外培养导致的潜在适应和亚群选择
成本高 个性化药物治疗
微流体模型 模拟了肿瘤细胞在体内复杂的微环境 成本高,技术复杂
器官芯片的制造尚未标准化
无法检测免疫细胞群在转移过程中的作用
高通量药物的筛选
加速药物开发及临床转化过程
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