人源胰腺癌类器官模型的构建及应用新进展

陈虹; 曹治云

doi:10.19401/j.cnki.1007-3639.2024.06.007

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人源胰腺癌类器官模型的构建及应用新进展

综述 | 更新时间：2025-12-31

- 人源胰腺癌类器官模型的构建及应用新进展
- Recent progress in the construction and application of patient-derived pancreatic cancer organoid models
- 中国癌症杂志 2024年34卷第6期页码：590-597
- 作者机构：
  
  1. 福建中医药大学中西医结合研究院，福建福州 350122
  2. 福建省中西医结合老年性疾病重点实验室，福建福州 350122
  3. 福建省高校中西医结合基础重点实验室，福建福州 350122
- 作者简介：
  
  [ "陈虹（ORCID：0009-0005-6889-077X），硕士。" ]
  曹治云（ORCID：0000-0002-4873-149X），研究员，博士研究生导师。E-mail: caozhiyun@fjtcm.edu.cn。
- 基金信息：
  
  漳州片仔癀药业股份有限公司横向联合项目(YHT-21104)
- DOI：10.19401/j.cnki.1007-3639.2024.06.007
  中图分类号： R735.9
- 收稿：2024-01-03，
  
  修回：2024-04-11，
  
  纸质出版：2024-06-30
- 稿件说明：
移动端阅览
陈虹, 曹治云. 人源胰腺癌类器官模型的构建及应用新进展[J]. 中国癌症杂志, 2024,34(6):590-597.

Hong CHEN, Zhiyun CAO. Recent progress in the construction and application of patient-derived pancreatic cancer organoid models[J]. China Oncology, 2024, 34(6): 590-597.
陈虹, 曹治云. 人源胰腺癌类器官模型的构建及应用新进展[J]. 中国癌症杂志, 2024,34(6):590-597. DOI： 10.19401/j.cnki.1007-3639.2024.06.007.

Hong CHEN, Zhiyun CAO. Recent progress in the construction and application of patient-derived pancreatic cancer organoid models[J]. China Oncology, 2024, 34(6): 590-597. DOI： 10.19401/j.cnki.1007-3639.2024.06.007.

摘要

胰腺癌严重威胁人类健康，其高度异质性和恶性表型使患者的5年生存率仅为7.2%。胰腺癌的发病机制及药物开发研究常依赖于传统的二维培养模型（细胞系）和患者来源异种移植瘤模型，但因细胞系缺乏肿瘤的三维环境和异质性特征，而异种移植瘤模型则存在培养时间长、成功率低、难以开展高通量药物筛选等问题，急需开发可高度反映胰腺癌特征和分子变异的三维培养模型。人源胰腺癌类器官作为近年发展起来的三维培养模型，是从组织样本中提取的多细胞单位，在机械和酶消化后嵌入细胞外基质凝胶中，可再现原患者的组织学特征及器官特点，甚至具有原器官的功能。随着胰腺癌类器官培养体系的不断发展及完善，其简便、经济及稳定的培养技术已经逐步建立，推动人源胰腺癌类器官的应用扩展到药物高通量筛选、个体化精准治疗、更深入的发病机制及针对性的药物开发研究。同时，人源胰腺癌类器官亦是胰腺癌临床分子分型研究的优势全新半体内模型，特别在针对研究高突变及高异质性患者的病因、分子特征、组织形态及体细胞突变负荷方面表现优越。大样本量人源胰腺癌类器官生物样本库的构建，将成为生物学、基础医学和临床肿瘤学研究的全新平台，有助于胰腺癌发病机制的深入研究及治疗策略的优化。人源胰腺癌类器官可再现临床患者特征的实验室模型的应用，将使药物筛选、发病机制研究、个体化治疗的实现成为可能。本文综述人源胰腺癌类器官的最新研究进展，希望该文为从事相关人源胰腺癌类器官研究的人员提供借鉴。

Abstract

Pancreatic cancer is a worldwide medical and health problem. Due to its high heterogeneity and malignant phenotype

the 5-year survival rate of pancreatic cancer is only 7.2%

which is a serious threat to human health. The biological mechanism and drug development research of pancreatic cancer often rely on the traditional two-dimensional culture models (cell lines) and patient-derived xenograft models. However

cell lines lack the three-dimensional environment and heterogeneity of the tumor

while xenograft models have the disadvantages of long culture time

low success rate and difficulty in carrying out high-throughput drug screening. There is an urgent need to develop three-dimensional culture models that can highly reflect the characteristics and molecular variation of pancreatic cancer. As a three-dimensional culture model developed in recent years

human-derived pancreatic cancer organoids are multicellular units extracted from tissue samples and embedded in extracellular matrix gels after mechanical and enzymatic digestion

which can reproduce the histological characteristics and organ characteristics of the original patient

and even have the functions of the original organ. With the continuous development and improvement of pancreatic cancer organoids culture system

its simple

economical and stable culture technology has been gradually established

which promotes the application of human pancreatic cancer organoids to high-throughput drug screening

individualized precision treatment and deeper pathogenesis and targeted drug development research. At the same time

human-derived pancreatic cancer organoids are also a novel semi-in vivo model for the study of clinical molecular typing of pancreatic cancer

especially for the study of etiology

molecular characteristics

histomorphology and somatic mutation burden of patients with high mutation rate and high heterogeneity. The construction of human pancreatic cancer organoid biobank with large sample size is a new platform for biology

basic medicine and clinical science oncology research

which provides a reliable resource for the in-depth study of the pathogenesis of pancreatic cancer and the development of treatment strategies. In summary

the research progress of human pancreatic cancer organoids promotes the application of laboratory models that recapitulate the characteristics of clinical patients

improves the connection between basic laboratory research and clinical patients

and provides clinical sources for drug screening

pathogenesis research

individualized treatment strategies and the construction of biobanks. Therefore

this article reviewed the latest research progress of human pancreatic cancer organoids

in order to provide reference for researchers engaged in the research of human pancreatic cancer organoids.

关键词

Keywords

references

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