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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2022, Vol. 42 Issue (6): 47-53    DOI: 10.13523/j.cb.2201029
综述     
肿瘤类器官在药物筛选和个性化用药中的研究进展*
杨换连1,邱飞1,2,3,**,王国权1,2,刁勇1,2,3
1.华侨大学医学院 泉州 362021
2.华侨大学生物医学学院 泉州 362021
3.分子药物教育部工程研究中心 泉州 362021
Progress in the Research and Application of Tumor Organoids in Drug Screening and Personalized Drug Treatment
YANG Huan-lian1,QIU Fei(),WANG Guo-quan1,2,3,**,DIAO Yong
1. School of Medicine, Huaqiao University, Quanzhou 362021, China
2. School of Biomedical Sciences, Huaqiao University, Quanzhou 362021, China
3. Engineering Research Center for Molecular Medicine of Ministry of Education, Quanzhou 362021, China
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摘要:

恶性肿瘤是影响人类生命健康的重大疾病之一,药物治疗是常见的治疗手段。近年来,“精准治疗”已经成为肿瘤治疗的趋势。要实现对恶性肿瘤有效、精准的药物治疗,药物筛选模型至关重要。肿瘤类器官是近年来新兴的一种三维细胞模型,具有经长期传代还保留亲本肿瘤的特征和异质性、培养成功率高、周期短和能够高通量筛选药物等优点,已被用于药物筛选、预测患者对治疗的反应以及为个性化用药提供指导等。重点介绍了肿瘤类器官在药物筛选及个性化用药中的研究进展和面临的挑战。

关键词: 肿瘤类器官药物筛选个性化用药精准治疗肿瘤    
Abstract:

Malignant tumor is one of the major diseases that threaten human life, and drug therapy is a common method. Currently, precision treatment has become a trend of tumor therapy. To achieve effective and precise drug therapy for malignant tumors, the drug screening models are very important points. Tumor organoids are three-dimensional cell models which have emerged in recent years. They have the advantages of retaining the characteristics and heterogeneity of parental tumors during long-term culture, with high success rate of culture and short culture cycle, and they can be used for high-throughput drug screening. They have been used for drug screening, predicting patients’ response of drug therapy, and providing guidance for personalized drug treatment. The progress of tumor organoids in drug screening and personalized drug treatment, and possible challenges were introduced.

Key words: Tumor organoids    Drug screening    Personalized drug treatment    Precision treatment    Tumor
收稿日期: 2022-01-21 出版日期: 2022-07-07
ZTFLH:  R965  
基金资助: *福建省自然科学基金(2018J01127)
通讯作者: 邱飞     E-mail: qiufei@hqu.edu.cn
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引用本文:

杨换连,邱飞,王国权,刁勇. 肿瘤类器官在药物筛选和个性化用药中的研究进展*[J]. 中国生物工程杂志, 2022, 42(6): 47-53.

YANG Huan-lian,QIU Fei,WANG Guo-quan,DIAO Yong. Progress in the Research and Application of Tumor Organoids in Drug Screening and Personalized Drug Treatment. China Biotechnology, 2022, 42(6): 47-53.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2201029        https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I6/47

图1  肿瘤类器官的应用
[1] Moffat J G, Rudolph J, Bailey D. Phenotypic screening in cancer drug discovery-past, present and future. Nature Reviews Drug Discovery, 2014, 13(8): 588-602.
doi: 10.1038/nrd4366 pmid: 25033736
[2] 高彤, 丁冠守, 苏萍萍, 等. 药物筛选模型的研究进展. 海峡药学, 2021, 33(7): 1-5.
Gao T, Ding G S, Su P P, et al. Advances in drug screening models. Strait Pharmaceutical Journal, 2021, 33(7): 1-5.
[3] Pauli C, Hopkins B D, Prandi D, et al. Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discovery, 2017, 7(5): 462-477.
doi: 10.1158/2159-8290.CD-16-1154
[4] Nguyen L V, Caldas C. Functional genomics approaches to improve pre-clinical drug screening and biomarker discovery. EMBO Molecular Medicine, 2021, 13(9): e13189.
[5] Tsimberidou A M, Fountzilas E, Nikanjam M, et al. Review of precision cancer medicine: evolution of the treatment paradigm. Cancer Treatment Reviews, 2020, 86: 102019.
doi: 10.1016/j.ctrv.2020.102019
[6] Chen Y J, Juan L R, Lv X, et al. Bioinformatics research on drug sensitivity prediction. Frontiers in Pharmacology, 2021, 12: 799712.
doi: 10.3389/fphar.2021.799712
[7] Huo K G, D’Arcangelo E, Tsao M S. Patient-derived cell line, xenograft and organoid models in lung cancer therapy. Translational Lung Cancer Research, 2020, 9(5): 2214-2232.
doi: 10.21037/tlcr-20-154
[8] Klinghammer K, Walther W, Hoffmann J. Choosing wisely-preclinical test models in the era of precision medicine. Cancer Treatment Reviews, 2017, 55: 36-45.
doi: S0305-7372(17)30028-2 pmid: 28314175
[9] Pyo D H, Hong H K, Lee W Y, et al. Patient-derived cancer modeling for precision medicine in colorectal cancer: beyond the cancer cell line. Cancer Biology & Therapy, 2020, 21(6): 495-502.
[10] Zhuo J Y, Su R Y, Tan W, et al. The ongoing trends of patient-derived xenograft models in oncology. Cancer Communications, 2020, 40(11): 559-563.
doi: 10.1002/cac2.12096
[11] Drost J, Clevers H. Organoids in cancer research. Nature Reviews Cancer, 2018, 18(7): 407-418.
doi: 10.1038/s41568-018-0007-6
[12] Chen H D, Zhuo Q F, Ye Z, et al. Organoid model: a new hope for pancreatic cancer treatment. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2021, 1875(1): 188466.
doi: 10.1016/j.bbcan.2020.188466
[13] Chan A S, Yan H H N, Leung S Y. Breakthrough moments: organoid models of cancer. Cell Stem Cell, 2019, 24(6): 839-840.
doi: 10.1016/j.stem.2019.05.006
[14] Kelly P N. Cancer organoids to model therapy response. Science, 2018, 359(6378): 880-881.
doi: 10.1126/science.2018.359.6378.twis
[15] Gao D, Vela I, Sboner A, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell, 2014, 159(1): 176-187.
doi: 10.1016/j.cell.2014.08.016
[16] Broutier L, Mastrogiovanni G, Verstegen M M, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nature Medicine, 2017, 23(12): 1424-1435.
doi: 10.1038/nm.4438 pmid: 29131160
[17] 冯紫伊, 梁珊珊, 于炜婷, 等. 患者来源肿瘤类器官的培养与研究及应用. 中国组织工程研究, 2021, 25(25): 4082-4088.
Feng Z Y, Liang S S, Yu W T, et al. Culture, research and application of patient-derived tumor organoids. Chinese Journal of Tissue Engineering Research, 2021, 25(25): 4082-4088.
[18] 高坚钧, 秦伟, 王浩, 等. 类器官技术在肿瘤研究中的应用与展望. 中国组织工程研究, 2019, 23(7): 1136-1141.
Gao J J, Qin W, Wang H, et al. Application and prospect of organoid technique in cancer research. Chinese Journal of Tissue Engineering Research, 2019, 23(7): 1136-1141.
[19] 李甜瑞, 赵瑞波, 张权, 等. 类器官及其应用的研究进展. 生物化学与生物物理进展, 2019, 46(8): 737-750.
Li T R, Zhao R B, Zhang Q, et al. Progress in the research of organoids and applications. Progress in Biochemistry and Biophysics, 2019, 46(8): 737-750.
[20] 张健. 基于转录组数据挖掘的肿瘤异质性与肿瘤免疫微环境研究. 北京: 军事科学院, 2019.
Zhang J. Mining large-scale tumor transcriptome profiles to inform cancer heterogeneity and immune microenvironment. Beijing: Academy of Military Sciences, 2019.
[21] Bonin S, Stanta G. Pre-analytics and tumor heterogeneity. New Biotechnology, 2020, 55: 30-35.
doi: 10.1016/j.nbt.2019.09.007
[22] Kim J. Cellular reprogramming to model and study epigenetic alterations in cancer. Stem Cell Research, 2020, 49: 102062.
doi: 10.1016/j.scr.2020.102062
[23] Tiriac H, Plenker D, Baker L A, et al. Organoid models for translational pancreatic cancer research. Current Opinion in Genetics & Development, 2019, 54: 7-11.
[24] Buzzelli J N, Ouaret D, Brown G, et al. Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance. Stem Cell Research, 2018, 27: 109-120.
doi: S1873-5061(18)30022-9 pmid: 29414601
[25] van de Wetering M, Francies H E, Francis J M, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell, 2015, 161(4): 933-945.
doi: 10.1016/j.cell.2015.03.053 pmid: 25957691
[26] Seidlitz T, Koo B K, Stange D E. Gastric organoids-an in vitro model system for the study of gastric development and road to personalized medicine. Cell Death & Differentiation, 2021, 28(1): 68-83.
[27] Frappart P O, Walter K, Gout J, et al. Pancreatic cancer-derived organoids - a disease modeling tool to predict drug response. United European Gastroenterology Journal, 2020, 8(5): 594-606.
doi: 10.1177/2050640620905183
[28] Lee S H, Hu W H, Matulay J T, et al. Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell, 2018, 173(2): 515-528, e17.
doi: 10.1016/j.cell.2018.03.017
[29] 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. Scientific Reports, 2020, 10(1): 12581.
doi: 10.1038/s41598-020-69488-9
[30] Saifuddin S R, Devlies W, Santaolalla A, et al. King’s health partners’ prostate cancer biobank (KHP PCaBB). BMC Cancer, 2017, 17(1): 784.
doi: 10.1186/s12885-017-3773-8 pmid: 29166865
[31] Kim M, Mun H, Sung C O, et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nature Communications, 2019, 10(1): 3991.
doi: 10.1038/s41467-019-11867-6
[32] Sachs N, de Ligt J, Kopper O, et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell, 2018, 172(1-2): 373-386, e10.
doi: 10.1016/j.cell.2017.11.010
[33] Kenny H A, Lal-Nag M, White E A, et al. Quantitative high throughput screening using a primary human three-dimensional organotypic culture predicts in vivo efficacy. Nature Communications, 2015, 6: 6220.
doi: 10.1038/ncomms7220
[34] Brancato V, Oliveira J M, Correlo V M, et al. Could 3D models of cancer enhance drug screening. Biomaterials, 2020, 232: 119744.
doi: 10.1016/j.biomaterials.2019.119744
[35] 颜畅, 胡艺冰, 赵晖, 等. CEA-TCB双特异性抗体cibisatamab增强T细胞对胃癌类器官的免疫杀伤作用. 华中科技大学学报(医学版), 2020, 49(5): 511-516.
Yan C, Hu Y B, Zhao H, et al. Effect of CEA-CD 3 bispecific antibody cibisatamab in enhancing T cells immunocompetence in gastric cancer organoids. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2020, 49(5): 511-516.
[36] Zumwalde N A, Haag J D, Sharma D, et al. Analysis of immune cells from human mammary ductal epithelial organoids reveals Vδ2+ T cells that efficiently target breast carcinoma cells in the presence of bisphosphonate. Cancer Prevention Research (Philadelphia, Pa), 2016, 9(4): 305-316.
[37] Cattaneo C M, Dijkstra K K, Fanchi L F, et al. Tumor organoid-T-cell coculture systems. Nature Protocols, 2020, 15(1): 15-39.
doi: 10.1038/s41596-019-0232-9 pmid: 31853056
[38] Litman T. Personalized medicine-concepts, technologies, and applications in inflammatory skin diseases. APMIS, 2019, 127(5): 386-424.
doi: 10.1111/apm.12934
[39] Goetz L H, Schork N J. Personalized medicine: motivation, challenges, and progress. Fertility and Sterility, 2018, 109(6): 952-963.
doi: 10.1016/j.fertnstert.2018.05.006
[40] Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science, 2018, 359(6378): 920-926.
doi: 10.1126/science.aao2774 pmid: 29472484
[41] Yan H H N, Siu H C, Law S, et al. A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening. Cell Stem Cell, 2018, 23(6): 882-897, e11.
doi: 10.1016/j.stem.2018.09.016
[42] Broekgaarden M, Rizvi I, Bulin A L, et al. Neoadjuvant photodynamic therapy augments immediate and prolonged oxaliplatin efficacy in metastatic pancreatic cancer organoids. Oncotarget, 2018, 9(16): 13009-13022.
doi: 10.18632/oncotarget.24425 pmid: 29560127
[43] Driehuis E, van Hoeck A, Moore K, et al. Pancreatic cancer organoids recapitulate disease and allow personalized drug screening. Proceedings of the National Academy of Sciences, 2019, 116(52): 26580-26590.
[44] Verissimo C S, Overmeer R M, Ponsioen B, et al. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening. eLife, 2016, 5: e18489.
doi: 10.7554/eLife.18489
[45] 路小欢, 徐鲁明, 王星月, 等. 结直肠癌类器官的构建与应用进展. 中华医学杂志, 2019, 99(36): 2878-2880.
Lu X H, Xu L M, Wang X Y, et al. Progress in the construction of colorectal cancer organoids and applications. National Medical Journal of China, 2019, 99(36): 2878-2880.
[46] Ooft S N, Weeber F, Schipper L, et al. Prospective experimental treatment of colorectal cancer patients based on organoid drug responses. ESMO Open, 2021, 6(3): 100103.
doi: 10.1016/j.esmoop.2021.100103
[47] Liu C, Qin T Y, Huang Y H, et al. Drug screening model meets cancer organoid technology. Translational Oncology, 2020, 13(11): 100840.
doi: 10.1016/j.tranon.2020.100840
[48] Yanagisawa K, Konno M, Liu H, et al. A four-dimensional organoid system to visualize cancer cell vascular invasion. Biology, 2020, 9(11): 361.
doi: 10.3390/biology9110361
[49] Dijkstra K K, Cattaneo C M, Weeber F, et al. Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids. Cell, 2018, 174(6): 1586-1598, e12.
doi: S0092-8674(18)30903-6 pmid: 30100188
[50] Li Y Q, Tang P Y, Cai S J, et al. Organoid based personalized medicine: from bench to bedside. Cell Regeneration (London, England), 2020, 9(1): 21.
[51] 罗升昌, 王颖, 王士斌, 等. 基于微流控技术构建3D肿瘤模型用于药物筛选. 科学通报, 2021, 66(34): 4395-4410.
Luo S C, Wang Y, Wang S B, et al. Construction of 3D-tumor model for drug screening: application of microfluidics. Chinese Science Bulletin, 2021, 66(34): 4395-4410.
[52] Kim E, Choi S, Kang B, et al. Creation of bladder assembloids mimicking tissue regeneration and cancer. Nature, 2020, 588(7839): 664-669.
doi: 10.1038/s41586-020-3034-x
[53] Ji D B, Wu A W. Organoid in colorectal cancer: progress and challenges. Chinese Medical Journal, 2020, 133(16): 1971-1977.
doi: 10.1097/CM9.0000000000000882
[54] Hu Y, Sui X, Song F, et al. Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week. Nature Communications, 2021, 12: 2581.
doi: 10.1038/s41467-021-22676-1
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