患者来源类器官模型在转移癌中的研究进展

doi:10.3760/cma.j.cn371439-20250901-00122

摘要/Abstract

摘要：

患者来源类器官（PDO）是由干细胞体外培养而来的能够自我组装的微观三维结构，可高度重现来源组织的结构、生理及遗传特征，与患者临床疗效高度相关。近年来，PDO模型已成为研究肿瘤转移机制及其治疗策略的理想工具。系统探讨PDO模型在不同类型肿瘤转移癌中的应用及最新研究进展，可为精准化抗肿瘤治疗策略提供重要的理论依据。

关键词: 类器官, 肿瘤转移, 精准医学, 抗药性

Abstract:

Patient-derived organoids （PDOs） are self-assembling， microscopic three-dimensional structures cultivated in vitro from stem cells. They can highly recapitulate the structural， physiological， and genetic characteristics of the original tissue and demonstrate a high correlation with patients' clinical efficacy. In recent years， PDOs models have emerged as an ideal tool for investigating the mechanisms of tumor metastasis and developing corresponding therapeutic strategies. Further exploration of the application and latest research progress regarding PDOs models in various types of metastatic cancers will provide a critical theoretical foundation for advancing precision anti-tumor treatment strategies.

Key words: Organoids, Neoplasm metastasis, Precision medicine, Drug resistance

于紫薇, 庄庆春, 孙静, 李新宇, 沙丹. 患者来源类器官模型在转移癌中的研究进展[J]. 国际肿瘤学杂志, 2025, 52(11): 714-719.

Yu Ziwei, Zhuang Qingchun, Sun Jing, Li Xinyu, Sha Dan. Research progress of patient-derived organoid models in metastatic cancer[J]. Journal of International Oncology, 2025, 52(11): 714-719.

参考文献 38

[1]	Li Y, Liu F, Cai Q, et al. Invasion and metastasis in cancer: molecular insights and therapeutic targets[J]. Signal Transduct Target Ther, 2025, 10(1): 57. DOI: 10.1038/s41392-025-02148-4.
[2]	Dai X, Xi M, Li J. Cancer metastasis: molecular mechanisms and therapeutic interventions[J]. Mol Biomed, 2025, 6(1): 20. DOI: 10.1186/s43556-025-00261-y. pmid: 40192949
[3]	Wang C, Nagayach A, Patel H, et al. Utilizing human cerebral organoids to model breast cancer brain metastasis in culture[J]. Breast Cancer Res, 2024, 26(1): 108. DOI: 10.1186/s13058-024-01865-y. pmid: 38951862
[4]	Pang M J, Burclaff JR, Jin R, et al. Gastric organoids: progress and remaining challenges[J]. Cell Mol Gastroenterol Hepatol, 2022, 13(1): 19-33. DOI: 10.1016/j.jcmgh.2021.09.005.
[5]	Zhou S, Lu J, Liu S, et al. Role of the tumor microenvironment in malignant melanoma organoids during the development and metastasis of tumors[J]. Front Cell Dev Biol, 2023, 11: 1166916. DOI: 10.3389/fcell.2023.1166916.
[6]	Abdolahi S, Ghazvinian Z, Muhammadnejad S, et al. Patient-derived xenograft (PDX) models, applications and challenges in cancer research[J]. J Transl Med, 2022, 20(1): 206. DOI: 10.1186/s12967-022-03405-8. pmid: 35538576
[7]	Park Y, Lee D, Lee JE, et al. The matrix stiffness coordinates the cell proliferation and PD-L1 expression via YAP in lung adenocarcinoma[J]. Cancers (Basel), 2024, 16(3): 598. DOI: 10.3390/cancers16030598.
[8]	Seidlitz T, Koo BK, Stange DE. Gastric organoids—an in vitro model system for the study of gastric development and road to personalized medicine[J]. Cell Death Differ, 2021, 28(1): 68-83. DOI: 10.1038/s41418-020-00662-2. pmid: 33223522
[9]	Paul CD, Yankaskas C, Shahi Thakuri P, et al. Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications[J]. Sci Rep, 2025, 15(1): 3933. DOI: 10.1038/s41598-025-86979-9.
[10]	Idrisova KF, Simon HU, Gomzikova MO. Role of patient-derived models of cancer in translational oncology[J]. Cancers (Basel), 2022, 15(1): 139. DOI: 10.3390/cancers15010139.
[11]	Pang X, Hu Y, Dai Z, et al. Precision medicine research progress based on colorectal cancer organoids[J]. Horm Cancer, 2025, 16(1): 1181. DOI: 10.1007/s12672-025-02959-5.
[12]	Cartry J, Bedja S, Boilève A, et al. Implementing patient derived organoids in functional precision medicine for patients with advanced colorectal cancer[J]. J Exp Clin Cancer Res, 2023, 42(1): 281. DOI: 10.1186/s13046-023-02853-4. pmid: 37880806
[13]	van de Wetering M, Francies HE, Francis JM, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients[J]. Cell, 2015, 161(4): 933-945. DOI: 10.1016/j.cell.2015.03.053. pmid: 25957691
[14]	Thng DKH, Hooi L, Siew BE, et al. A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids[J]. NPJ Precis Oncol, 2024, 8(1): 52. DOI: 10.1038/s41698-024-00543-8. pmid: 38413740
[15]	Sachs N, de Ligt J, Kopper O, et al. A living biobank of breast cancer organoids captures disease heterogeneity[J]. Cell, 2018, 172(1/2): 373-386.e10. DOI: 10.1016/j.cell.2017.11.010.
[16]	Yan HH, Siu HC, Law S, et al. A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening[J]. Cell Stem Cell, 2018, 23(6): 882-897.e11. DOI: 10.1016/j.stem.2018.09.016. pmid: 30344100
[17]	Liu Y, Lankadasari M, Rosiene J, et al. Modeling lung adenocarcinoma metastases using patient-derived organoids[J]. Cell Rep Med, 2024, 5(10): 101777. DOI: 10.1016/j.xcrm.2024.101777.
[18]	Buzzelli JN, Ouaret D, Brown G, et al. Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance[J]. Stem Cell Res, 2018, 27: 109-120. DOI: 10.1016/j.scr.2018.01.016. pmid: 29414601
[19]	Chen J, Cheng S, Gu L, et al. Establishment and characterization of a sigmoid colon cancer organoid with spinal metastasis[J]. Front Cell Dev Biol, 2025, 12: 1510264. DOI: 10.3389/fcell.2024.1510264.
[20]	Wang L, Hu XD, Li SY, et al. ASPM facilitates colorectal cancer cells migration and invasion by enhancing β-catenin expression and nuclear translocation[J]. Kaohsiung J Med Sci, 2022, 38(2): 129-138. DOI: 10.1002/kjm2.12464.
[21]	Morita A, Nakayama M, Wang D, et al. Frequent loss of metastatic ability in subclones of Apc, Kras, Tgfbr2, and Trp53 mutant intestinal tumor organoids[J]. Cancer Sci, 2023, 114(4): 1437-1450. DOI: 10.1111/cas.15709.
[22]	Gao D, Vela I, Sboner A, et al. Organoid cultures derived from patients with advanced prostate cancer[J]. Cell, 2014, 159(1): 176-187. DOI: 10.1016/j.cell.2014.08.016. pmid: 25201530
[23]	Mout L, van Dessel LF, Kraan J, et al. Generating human prostate cancer organoids from leukapheresis enriched circulating tumour cells[J]. Eur J Cancer, 2021, 150: 179-189. DOI: 10.1016/j.ejca.2021.03.023. pmid: 33932725
[24]	Lin KC, Ting LL, Chang CL, et al. Ex vivo expanded circulating tumor cells for clinical anti-cancer drug prediction in patients with head and neck cancer[J]. Cancers (Basel), 2021, 13(23): 6076. DOI: 10.3390/cancers13236076.
[25]	De Angelis ML, Francescangeli F, Nicolazzo C, et al. An organoid model of colorectal circulating tumor cells with stem cell features, hybrid EMT state and distinctive therapy response profile[J]. J Exp Clin Cancer Res, 2022, 41(1): 86. DOI: 10.1186/s13046-022-02263-y. pmid: 35260172
[26]	Wu YH, Chao HS, Chiang CL, et al. Personalized cancer avatars for patients with thymic malignancies: a pilot study with circulating tumor cell-derived organoids[J]. Thorac Cancer, 2023, 14(25): 2591-2600. DOI: 10.1111/1759-7714.15039.
[27]	Mo S, Tang P, Luo W, et al. Patient-derived organoids from colorectal cancer with paired liver metastasis reveal tumor heterogeneity and predict response to chemotherapy[J]. Adv Sci (Weinh), 2022, 9(31): e2204097. DOI: 10.1002/advs.202204097.
[28]	Ubink I, Bolhaqueiro ACF, Elias SG, et al. Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy[J]. Br J Surg, 2019, 106(10): 1404-1414. DOI: 10.1002/bjs.11206. pmid: 31197820
[29]	Mönch D, Koch J, Maaß A, et al. A human ex vivo coculture model to investigate peritoneal metastasis and innovative treatment options[J]. Pleura Peritoneum, 2021, 6(3): 121-129. DOI: 10.1515/pp-2021-0128. pmid: 34676285
[30]	Önder CE, Ziegler TJ, Becker R, et al. Advancing cancer therapy predictions with patient-derived organoid models of metastatic breast cancer[J]. Cancers (Basel), 2023, 15(14): 3602. DOI: 10.3390/cancers15143602.
[31]	Cheng F, Li P, Xu S, et al. A pair of primary colorectal cancer-derived and corresponding synchronous liver metastasis-derived organoid cell lines[J]. Aging (Albany NY), 2024, 16(5): 4396-4422. DOI: 10.18632/aging.205595.
[32]	Hicks WH, Gattie LC, Shami ME, et al. Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy[J]. Sci Rep, 2024, 14(1): 24843. DOI: 10.1038/s41598-024-76583-8. pmid: 39438602
[33]	焦盼盼, 薛丽娟, 詹娟. 免疫检查点抑制剂相关不良反应的危险因素与预测因素[J]. 国际肿瘤学杂志, 2023, 50(12): 739-744. DOI: 10.3760/cma.j.cn371439-20230810-00139.
[34]	Küçükköse E, Heesters BA, Villaudy J, et al. Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice[J]. J Immunother Cancer, 2022, 10(12): e005345. DOI: 10.1136/jitc-2022-005345.
[35]	Wang J, Tao X, Zhu J, et al. Tumor organoid-immune co-culture models: exploring a new perspective of tumor immunity[J]. Cell Death Discov, 2025, 11(1): 195. DOI: 10.1038/s41420-025-02407-x. pmid: 40268893
[36]	Zhou X, Qu M, Tebon P, et al. Screening cancer immunotherapy: when engineering approaches meet artificial intelligence[J]. Adv Sci (Weinh), 2020, 7(19): 2001447. DOI: 10.1002/advs.202001447.
[37]	Zhou R, Brislinger D, Fuchs J, et al. Vascularised organoids: recent advances and applications in cancer research[J]. Clin Transl Med, 2025, 15(3): e70258. DOI: 10.1002/ctm2.70258.
[38]	Hajal C, Ibrahim L, Serrano JC, et al. The effects of luminal and trans-endothelial fluid flows on the extravasation and tissue invasion of tumor cells in a 3D in vitro microvascular platform[J]. Biomaterials, 2021, 265: 120470. DOI: 10.1016/j.biomaterials.2020.120470.