类器官在妇科恶性肿瘤药物筛选中的应用

蒋媛媛; 魏文斐; 吴靖雅; 黎华文

doi:10.19401/j.cnki.1007-3639.2024.11.008

您当前的位置：

首页 >

文章列表页 >

类器官在妇科恶性肿瘤药物筛选中的应用

综述 | 更新时间：2025-12-31

- 类器官在妇科恶性肿瘤药物筛选中的应用
- Application of organoids in drug screening of gynecological malignant tumors
- 中国癌症杂志 2024年34卷第11期页码：1053-1060
- 作者机构：
  
  1. 广东医科大学第一临床医学院，广东湛江 524023
  2. 暨南大学珠海临床医学院（珠海市人民医院）妇科，广东珠海 519000
- 作者简介：
  
  [ "蒋媛媛（ORCID: 0009-0001-5351-6313），硕士。" ]
  黎华文（ORCID: 0000-0002-4126-354X），博士，主任医师，暨南大学珠海临床医学院（珠海市人民医院）妇科主任、妇产科教研室主任。
- 基金信息：
  
  广州市科技计划市校联合资助项目(SL2022A03J00449);广东省医学科学技术研究基金项目(A2023203)
- DOI：10.19401/j.cnki.1007-3639.2024.11.008
  中图分类号： R737.3
- 收稿：2024-09-23，
  
  修回：2024-11-10，
  
  纸质出版：2024-11-30
- 稿件说明：
移动端阅览
蒋媛媛, 魏文斐, 吴靖雅, 等. 类器官在妇科恶性肿瘤药物筛选中的应用[J]. 中国癌症杂志, 2024,34(11):1053-1060.

Yuanyuan JIANG, Wenfei WEI, Jingya WU, et al. Application of organoids in drug screening of gynecological malignant tumors[J]. China Oncology, 2024, 34(11): 1053-1060.
蒋媛媛, 魏文斐, 吴靖雅, 等. 类器官在妇科恶性肿瘤药物筛选中的应用[J]. 中国癌症杂志, 2024,34(11):1053-1060. DOI： 10.19401/j.cnki.1007-3639.2024.11.008.

Yuanyuan JIANG, Wenfei WEI, Jingya WU, et al. Application of organoids in drug screening of gynecological malignant tumors[J]. China Oncology, 2024, 34(11): 1053-1060. DOI： 10.19401/j.cnki.1007-3639.2024.11.008.

摘要

妇科恶性肿瘤是威胁女性生命健康的重大疾病之一，其发病率和死亡率在女性各类疾病中均位居前列。妇科恶性肿瘤起源于女性生殖器官，通常依据发病部位进行分类，其中卵巢癌（ovarian cancer，OC）、子宫内膜癌（endometrial cancer，EC）及宫颈癌（cervical cancer，CCA）是较为常见的几种类型。目前妇科恶性肿瘤多采用以手术、化疗及放疗为主的综合治疗，其中药物在治疗过程中发挥着至关重要的作用。然而，实际临床治疗效果常受到多种因素影响，如药物毒性导致的不良反应和部分患者对药物的耐药性、不敏感性，这些因素都限制了患者生存率的提高。最新研究表明，同一类型的肿瘤在不同个体间呈现出显著的生物学特性和药物反应异质性，这是导致临床上对同一种妇科恶性肿瘤采用相同药物治疗方法却产生不同治疗效果的重要原因。因此，为了实现妇科恶性肿瘤的个体化精准治疗，迫切需要建立与人类肿瘤高度相似的体外模型进行临床研究。药物筛选是一种用于识别和评估具有药物活性及潜在治疗作用化合物的技术，其通过对不同药物在特定条件下的作用效果进行评估，可为医师提供科学的用药指导，避免盲目试药，减少患者的治疗痛苦和经济负担。类器官模型作为药物筛选和个性化医疗的一种创新手段，在探究妇科恶性肿瘤治疗方面进行了广泛研究。类器官是一种在体外由干细胞进行三维培养而形成的具有一定空间结构的组织类似物，能高度模拟体内组织结构及功能，并展现出与人体器官极为相似的组织学和基因型特征。它在很大程度上克服了患者源性癌细胞模型、患者源性异种移植瘤模型等传统肿瘤模型的局限性，已成为肿瘤学领域的重要研究工具，为妇科恶性肿瘤药物筛选研究搭建了一个更具生理学相关性的实验平台。因此，本文将对几种临床前癌症模型的优缺点进行比较，回顾类器官技术的发展历程，阐述妇科肿瘤类器官的建立以及其在OC、EC及CCA药物筛选中的应用，同时探讨类器官技术在当前应用中存在的局限性和未来的发展愿景，旨在为未来的医学研究，特别是新药研究和个性化医疗研究带来启示。

Abstract

Gynecologic malignant tumors are among the leading diseases threatening women’s lives and health

with the highest morbidity and mortality rates among all female diseases. These tumors originate from female reproductive organs and are typically classified based on the affected site. Ovarian cancer (OC)

endometrial cancer (EC) and cervical cancer (CCA) are the most common types. Currently

gynecologic malignant tumors are primarily treated with a combination of surgery

chemotherapy and radiotherapy

where drugs play a critical role in the treatment process. However

the actual clinical effectiveness is often influenced by various factors

such as adverse reactions due to drug toxicity and the drug resistance and insensitivity observed in some patients

which limit improvements in patient survival rates. Recent studies have shown that the same type of tumor exhibits significant biological characteristics and drug response heterogeneity among different individuals

which is a key factor contributing to the varied clinical outcomes when using the same drug treatment for the same type of gynecologic malignant tumor. To achieve individualized and precise treatment for gynecologic malignant tumors

there is an urgent need to develop in vitro models that closely resemble human tumors for clinical research. Drug screening is a technique used to identify and evaluate compounds with pharmacological activity and potential therapeutic effects

providing doctors with scientific guidance on drug use

thereby avoiding blind drug testing and reducing patients' therapeutic pain and economic burden by assessing the effects of different drugs under specific conditions. Organoid models have been extensively studied as an innovative drug screening tool and personalized medicine for treating gynecologic malignancies. Organoids are tissue-like structures with a specific spatial arrangement formed in vitro through three-dimensional cell culture

capable of highly simulating the structure and function of tissues in vivo and displaying histological and genotypic characteristics very similar to human organs. This approach has largely overcome the limitations of traditional tumor models

such as patient-derived cancer cell models and patient-derived tumor xenograft models

becoming an essential research tool in oncology. It provides a more physiologically relevant experimental platform for drug screening studies of gynecologic malignancies. This paper compared the advantages and disadvantages of several preclinical cancer models

reviewed the development process of organoids

and described the establishment of gynecologic oncology organoids and their application in drug screening for ovarian

endometrial

and cervical cancers. Additionally

we discussed the current limitations of organoid technology in its application and envisioned its future development

aiming to provide insights for future medical research

particularly in new drug discovery and personalized medicine.

关键词

Keywords

references

HAN B F , ZHENG R S , ZENG H M , et al. Cancer incidence and mortality in China, 2022 [J ] . J Natl Cancer Cent , 2024 , 4 ( 1 ): 47 - 53 .

孙雅倩 . 三维细胞模型在抗癌药物筛选中的研究进展 [J ] . 现代诊断与治疗 , 2023 , 34 ( 11 ): 1629 - 1631 .

SUN Y Q . Research progress of 3D cell model in anti-cancer drug screening [J ] . Mod Diagn Treat , 2023 , 34 ( 11 ): 1629 - 1631 .

张宁 , 杨慧 , 王鹏 . 类器官在癌症研究、药物筛选与精准诊疗中的应用进展 [J ] . 北京大学学报(医学版) , 2022 , 54 ( 5 ): 814 - 21 .

ZHANG N , YANG H , WANG P . Advances in the application of organoids in cancer research, drug screening, and precision diagnosis and treatment [J ] . J Peking Univ (Health Sci) , 2022 , 54 ( 5 ): 814 - 21 .

LIU Y H , WU W T , CAI C J , et al. Patient-derived xenograft models in cancer therapy: technologies and applications [J ] . Signal Transduct Target Ther , 2023 , 8 ( 1 ): 160 .

JIN J K , YOSHIMURA K , SEWASTJANOW-SILVA M , et al. Challenges and prospects of patient-derived xenografts for cancer research [J ] . Cancers , 2023 , 15 ( 17 ): 4352 .

ZANELLA E R , GRASSI E , TRUSOLINO L . Towards precision oncology with patient-derived xenografts [J ] . Nat Rev Clin Oncol , 2022 , 19 ( 11 ): 719 - 732 . DOI: 10.1038/s41571-022-00682-6 http://doi.org/10.1038/s41571-022-00682-6

CHEN H D , ZHUO Q F , YE Z , et al. Organoid model: a new hope for pancreatic cancer treatment? [J ] . Biochim Biophys Acta Rev Cancer , 2021 , 1875 ( 1 ): 188466 .

ZHAO Z X , CHEN X Y , DOWBAJ A M , et al. Organoids [J ] . Nat Rev Methods Primers , 2022 , 2 : 94 .

GÓMEZ-ÁLVAREZ M , AGUSTINA-HERNÁNDEZ M , FRANCÉS-HERRERO E , et al. Addressing key questions in organoid models: who, where, how, and why? [J ] . Int J Mol Sci , 2023 , 24 ( 21 ): 16014 .

WILSON H V . A new method by which sponges may be artificially reared [J ] . Science , 1907 , 25 ( 649 ): 912 - 915 .

PELLEGRINI G , TRAVERSO C E , FRANZI A T , et al. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium [J ] . Lancet , 1997 , 349 ( 9057 ): 990 - 993 . DOI: 10.1016/S0140-6736(96)11188-0 http://doi.org/10.1016/S0140-6736(96)11188-0

SATO T , VRIES R G , SNIPPERT H J , et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche [J ] . Nature , 2009 , 459 ( 7244 ): 262 - 265 .

Method of the year 2017: organoids [J ] . Nat Meth , 2018 , 15 : 1 .

The United States Congress. S. 5002 (117th): FDA modernization Act 2.0[R/OL]. 2022[2024-01-01].

YUKI K , CHENG N , NAKANO M , et al. Organoid models of tumor immunology [J ] . Trends Immunol , 2020 , 41 ( 8 ): 652 - 664 . DOI: S1471-4906(20)30134-4 http://doi.org/S1471-4906(20)30134-4

SUN C P , LAN H R , FANG X L , et al. Organoid models for precision cancer immunotherapy [J ] . Front Immunol , 2022 , 13 : 770465 .

KOPPER O , DE WITTE C J , LÕHMUSSAAR K , et al. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity [J ] . Nat Med , 2019 , 25 ( 5 ): 838 - 849 . DOI: 10.1038/s41591-019-0422-6 http://doi.org/10.1038/s41591-019-0422-6

RINEHART C A JR , LYN-COOK B D , KAUFMAN D G . Gland formation from human endometrial epithelial cells in vitro [J ] . In Vitro Cell Dev Biol , 1988 , 24 ( 10 ): 1037 - 1041 .

MARU Y , TANAKA N , ITAMI M , et al. Efficient use of patient-derived organoids as a preclinical model for gynecologic tumors [J ] . Gynecol Oncol , 2019 , 154 ( 1 ): 189 - 198 . DOI: S0090-8258(19)31230-2 http://doi.org/S0090-8258(19)31230-2

BORETTO M , MAENHOUDT N , LUO X L , et al. Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening [J ] . Nat Cell Biol , 2019 , 21 ( 8 ): 1041 - 1051 . DOI: 10.1038/s41556-019-0360-z http://doi.org/10.1038/s41556-019-0360-z

MARU Y , TANAKA N , EBISAWA K , et al. Establishment and characterization of patient-derived organoids from a young patient with cervical clear cell carcinoma [J ] . Cancer Sci , 2019 , 110 ( 9 ): 2992 - 3005 .

NEAL J T , LI X N , ZHU J J , et al. Organoid modeling of the tumor immune microenvironment [J ] . Cell , 2018 , 175 ( 7 ): 1972 - 1988 .e16. DOI: S0092-8674(18)31513-7 http://doi.org/S0092-8674(18)31513-7

俞东红 , 曹华 , 王心睿 . 类器官的研究进展及应用 [J ] . 生物工程学报 , 2021 , 37 ( 11 ): 3961 - 3974 .

YU D H , CAO H , WANG X R . Advances and applications of organoids: a review [J ] . Chin J Biotechnol , 2021 , 37 ( 11 ): 3961 - 3974 .

DONG M , BÖPPLE K , THIEL J , et al. Perfusion air culture of precision-cut tumor slices: an ex vivo system to evaluate individual drug response under controlled culture conditions [J ] . Cells , 2023 , 12 ( 5 ): 807 .

TIAN J W , YANG J , CHEN T W , et al. Generation of human endometrial assembloids with a luminal epithelium using air-liquid interface culture methods [J ] . Adv Sci , 2023 , 10 ( 30 ): e2301868 .

QU J J , KALYANI F S , LIU L , et al. Tumor organoids: synergistic applications, current challenges, and future prospects in cancer therapy [J ] . Cancer Commun , 2021 , 41 ( 12 ): 1331 - 1353 .

PHAN N , HONG J J , TOFIG B , et al. A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids [J ] . Commun Biol , 2019 , 2 : 78 . DOI: 10.1038/s42003-019-0305-x http://doi.org/10.1038/s42003-019-0305-x

GOTIMER K , CHEN H , LEISEROWITZ G S , et al. Short-term organoid culture for drug sensitivity testing in high-grade serous ovarian cancer [J ] . Gynecol Oncol , 2019 , 153 ( 3 ): e13 .

NANKI Y , CHIYODA T , HIRASAWA A , et al. Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing [J ] . Sci Rep , 2020 , 10 ( 1 ): 12581 . DOI: 10.1038/s41598-020-69488-9 http://doi.org/10.1038/s41598-020-69488-9

HILL S J , DECKER B , ROBERTS E A , et al. Prediction of DNA repair inhibitor response in short-term patient-derived ovarian cancer organoids [J ] . Cancer Discov , 2018 , 8 ( 11 ): 1404 - 1421 . DOI: 10.1158/2159-8290.CD-18-0474 http://doi.org/10.1158/2159-8290.CD-18-0474

MAENHOUDT N , DEFRAYE C , BORETTO M , et al. Developing organoids from ovarian cancer as experimental and preclinical models [J ] . Stem Cell Reports , 2020 , 14 ( 4 ): 717 - 729 . DOI: S2213-6711(20)30094-1 http://doi.org/S2213-6711(20)30094-1

DE WITTE C J , et al. ESPEJO VALLE-INCLAN J, HAMI N, Patient-derived ovarian cancer organoids mimic clinical response and exhibit heterogeneous inter- and intrapatient drug responses [J ] . Cell Rep , 2020 , 31 ( 11 ): 107762 .

BAR-EPHRAIM Y E , KRETZSCHMAR K , CLEVERS H . Organoids in immunological research [J ] . Nat Rev Immunol , 2020 , 20 ( 5 ): 279 - 293 .

中国抗癌协会妇科肿瘤专业委员会 . 妇科恶性肿瘤多学科诊疗中国专家共识(2022年版) [J ] 中国癌症杂志 . 2022 , 32 ( 8 ): 747 - 56 . DOI: 10.19401/j.cnki.1007-3639.2022.08.010 http://doi.org/10.19401/j.cnki.1007-3639.2022.08.010

China Anti-Cancer Association Gynecologic Oncology Professional Committee . Consensus of Chinese experts on multidisciplinary team of gynecological malignant tumors (2022 edition) [J ] . China Oncology , 2022 , 32 ( 8 ): 747 - 56 . DOI: 10.19401/j.cnki.1007-3639.2022.08.010 http://doi.org/10.19401/j.cnki.1007-3639.2022.08.010

HIGA A , TAKAHASHI N , HIYAMA G , et al. High-throughput in vitro assay using patient-derived tumor organoids [J ] . J Vis Exp , 2021 , ( 172 ).

GIRDA E , HUANG E C , LEISEROWITZ G S , et al. The use of endometrial cancer patient-derived organoid culture for drug sensitivity testing is feasible [J ] . Int J Gynecol Cancer , 2017 , 27 ( 8 ): 1701 - 1707 . DOI: 10.1097/IGC.0000000000001061 http://doi.org/10.1097/IGC.0000000000001061

TAMURA H , HIGA A , HOSHI H , et al. Evaluation of anticancer agents using patient-derived tumor organoids characteristically similar to source tissues [J ] . Oncol Rep , 2018 , 40 ( 2 ): 635 - 646 . DOI: 10.3892/or.2018.6501 http://doi.org/10.3892/or.2018.6501

DAS S , BABU A , MEDHA T , et al. Molecular mechanisms augmenting resistance to current therapies in clinics among cervical cancer patients [J ] . Med Oncol , 2023 , 40 ( 5 ): 149 . DOI: 10.1007/s12032-023-01997-9 http://doi.org/10.1007/s12032-023-01997-9

SEOL H S , OH J H , CHOI E , et al. Preclinical investigation of patient-derived cervical cancer organoids for precision medicine [J ] . J Gynecol Oncol , 2023 , 34 ( 3 ): e35 .

FONG E L S , TOH T B , LIN Q X X , et al. Generation of matched patient-derived xenograft in vitro - in vivo models using 3D macroporous hydrogels for the study of liver cancer [J ] . Biomaterials , 2018 , 159 : 229 - 240 .

BORETTO M , COX B , NOBEN M , et al. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability [J ] . Development , 2017 , 144 ( 10 ): 1775 - 1786 . DOI: 10.1242/dev.148478 http://doi.org/10.1242/dev.148478

MARX V . Closing in on cancer heterogeneity with organoids [J ] . Nat Methods , 2024 , 21 ( 4 ): 551 - 554 .

GODBOLE N , QUINN A , CARRION F , et al. Extracellular vesicles as a potential delivery platform for CRISPR-Cas based therapy in epithelial ovarian cancer [J ] . Semin Cancer Biol , 2023 , 96 : 64 - 81 . DOI: 10.1016/j.semcancer.2023.10.002 http://doi.org/10.1016/j.semcancer.2023.10.002

BUCKLEY D N , LEWINGER J P , GOODEN G , et al. OvaPrint-a cell-free DNA methylation liquid biopsy for the risk assessment of high-grade serous ovarian cancer [J ] . Clin Cancer Res , 2023 , 29 ( 24 ): 5196 - 5206 .

SHI H Y , KOWALCZEWSKI A , VU D , et al. Organoid intelligence: integration of organoid technology and artificial intelligence in the new era of in vitro models [J ] . Med Nov Technol Devices , 2024 , 21 : 100276 .

YAO Q G , CHENG S , PAN Q L , et al. Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine [J ] . MedComm , 2024 , 5 ( 10 ): e735 . DOI: 10.1002/mco2.735 http://doi.org/10.1002/mco2.735

浏览量

1292

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

生物3D打印在肿瘤研究及组织工程中的应用

人源胰腺癌类器官模型的构建及应用新进展

利用单细胞测序和转录组测序建立结直肠癌免疫细胞的9基因预后模型

人工智能在类器官研究中的应用进展与挑战

类器官在肿瘤转化医学中的应用和进展