Application of Gastric Cancer Organoids in Precision Medicine Research

doi:10.12300/j.issn.1674-5817.2021.159

Abstract

Abstract:

Organoid is an in vitro three-dimensional culture system of stem cells or tissues derived from patients. Both normal gastric organoids and gastric cancer organoids can be established through this culture technique. Organoid possesses high fidelity, it grows with the similar molecular structures, functional characteristics, and genetic information as its tissue-of-origin. According to above, organoid can perform therapeutic targets screen, facilitate drug responses prediction and verification. Meanwhile, it also provides a new idea for precision medicine research of gastric cancer and replacement research of laboratory animals. This paper reviewed the establishment of organoid model of gastric cancer and the development of application of organoid in precision medicine, to provide ideal in vitro models reference for precision medicine research of gastric cancer.

Key words: Gastric cancer, Organoid, Precision medicine, Drug screening, Individualized treatment, Replacement

CLC Number:

R-332

Miaomiao GONG, Ligui ZHOU, Jumei ZHAO, Changhong SHI. Application of Gastric Cancer Organoids in Precision Medicine Research[J]. Laboratory Animal and Comparative Medicine, 2022, 42(3): 248-254.

Figures/Tables 2

References 45

1	BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer J Clin, 2018, 68(6):394-424. DOI:10.3322/caac.21492 .
2	HE Y, WANG Y, LUAN F, et al. Chinese and global burdens of gastric cancer from 1990 to 2019[J]. Cancer Med, 2021, 10(10):3461-3473. DOI:10.1002/cam4.3892 .
3	KERSTEN K, DE VISSER K E, VAN MILTENBURG M H, et al. Genetically engineered mouse models in oncology research and cancer medicine[J]. EMBO Mol Med, 2017, 9(2):137-153. DOI:10.15252/emmm.201606857 .
4	KIM J, KOO B K, KNOBLICH J A. Human organoids: model systems for human biology and medicine[J]. Nat Rev Mol Cell Biol, 2020, 21(10):571-584. DOI:10.1038/s41580-020-0259-3 .
5	RISBRIDGER G P, LAWRENCE M G, TAYLOR R A. PDX: moving beyond drug screening to versatile models for research discovery[J]. J Endocr Soc, 2020, 4(11): bvaa132. DOI:10.1210/jendso/bvaa132 .
6	CORRÒ C, NOVELLASDEMUNT L, LI V S W. A brief history of organoids[J]. Am J Physiol Cell Physiol, 2020, 319(1): C151-C165. DOI:10.1152/ajpcell.00120.2020 .
7	KAMB A. What's wrong with our cancer models?[J]. Nat Rev Drug Discov, 2005, 4(2):161-165. DOI:10.1038/nrd1635 .
8	CAPONIGRO G, SELLERS W R. Advances in the preclinical testing of cancer therapeutic hypotheses[J]. Nat Rev Drug Discov, 2011, 10(3):179-187. DOI:10.1038/nrd3385 .
9	VLACHOGIANNIS G, HEDAYAT S, VATSIOU A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers[J]. Science, 2018, 359(6378):920-926. DOI:10.1126/science.aao2774 .
10	SEIDLITZ T, MERKER S R, ROTHE A, et al. Human gastric cancer modelling using organoids[J]. Gut, 2019, 68(2):207-217. DOI:10.1136/gutjnl-2017-314549 .
11	JABS J, ZICKGRAF F M, PARK J, et al. Screening drug effects in patient-derived cancer cells links organoid responses to genome alterations[J]. Mol Syst Biol, 2017, 13(11):955. DOI:10.15252/msb.20177697 .
12	ABBASI J. Patient-derived organoids predict cancer treatment response[J]. JAMA, 2018, 319(14):1427. DOI:10.1001/jama.2018.3760 .
13	STEELE N G, CHAKRABARTI J, WANG J, et al. An organoid-based preclinical model of human gastric cancer[J]. Cell Mol Gastroenterol Hepatol, 2019, 7(1):161-184. DOI:10.1016/j.jcmgh.2018.09.008 .
14	BARKER N, HUCH M, KUJALA P, et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro [J]. Cell Stem Cell, 2010, 6(1):25-36. DOI:10.1016/j.stem.2009.11.013 .
15	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[J]. Cell Stem Cell, 2018, 23(6):882-897.e11. DOI:10.1016/j.stem. 2018.09.016 .
16	NANKI K, TOSHIMITSU K, TAKANO A, et al. Divergent routes toward wnt and R-spondin niche independency during human gastric carcinogenesis[J]. Cell, 2018, 174(4):856-869.e17. DOI:10.1016/j.cell.2018.07.027 .
17	GAO M, LIN M, RAO M, et al. Development of patient-derived gastric cancer organoids from endoscopic biopsies and surgical tissues[J]. Ann Surg Oncol, 2018, 25(9):2767-2775. DOI:10.1245/s10434-018-6662-8 .
18	UKAI S, HONMA R, SAKAMOTO N, et al. Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS₃ contributes to the attainment of features of cancer stem cell[J]. Oncogene, 2020, 39(50):7265-7278. DOI:10.1038/s41388-020-01492-9 .
19	HOLOKAI L, CHAKRABARTI J, BRODA T, et al. Increased programmed death-ligand 1 is an early epithelial cell response to Helicobacter pylori infection[J]. PLoS Pathog, 2019, 15(1): e1007468. DOI:10.1371/journal.ppat.1007468 .
20	STANGE D E, KOO B K, HUCH M, et al. Differentiated Troy+chief cells act as reserve stem cells to generate all lineages of the stomach epithelium[J]. Cell, 2013, 155(2):357-368. DOI:10.1016/j.cell.2013.09.008 .
21	XIAO X, CHEN W, WEI Z W, et al. The anti-tumor effect of nab-paclitaxel proven by patient-derived organoids[J]. Onco Targets Ther, 2020, 13:6017-6025. DOI:10.2147/ott.s237431 .
22	LI J, XU H, ZHANG L, et al. Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening[J]. J Cancer Res Clin Oncol, 2019, 145(11):2637-2647. DOI:10.1007/s00432-019-03004-z .
23	LAUREN P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification[J]. Acta Pathol Microbiol Scand, 1965, 64:31-49. DOI:10.1111/apm.1965.64.1.31 .
24	BOSMAN F T,　 CARNEIRO F,　 HRUBAN R H,　et al. WHO classification of tumours of the digestive system[M]. Lyon, France: International Agency for Research on Cancer Press, 2010.
25	CANCER GENOME ATLAS RESEARCH NETWORK. Comprehensive molecular characterization of gastric adenocarcinoma[J]. Nature, 2014, 513(7517):202-209. DOI:10.1038/nature13480 .
26	WANG K, YUEN S T, XU J, et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer[J]. Nat Genet, 2014, 46(6):573-582. DOI:10.1038/ng.2983 .
27	LO Y H,　 KOLAHI K,　 DU Y,　et al. A CRISPR/Cas9-engineered ARID1A-deficient human gastric cancer organoid model reveals essential and non-essential modes of oncogenic transformation[J]. Cancer Discov, 2021, 11(6):1562-1581. DOI: 10.1158/2159-8290.CD-20-1109 .
28	WANG Y, KIM R, GUNASEKARA D B, et al. Formation of human colonic crypt array by application of chemical gradients across a shaped epithelial monolayer[J]. Cell Mol Gastroenterol Hepatol, 2018, 5(2):113-130. DOI:10.1016/j.jcmgh.2017.10.007 .
29	WANG X, YAMAMOTO Y, WILSON L H, et al. Cloning and variation of ground state intestinal stem cells[J]. Nature, 2015, 522(7555):173-178. DOI:10.1038/nature14484 .
30	NAKAGAWA H, FUJITA M. Whole genome sequencing analysis for cancer genomics and precision medicine[J]. Cancer Sci, 2018, 109(3):513-522. DOI:10.1111/cas.13505 .
31	BARTFELD S, BAYRAM T, VAN DE WETERING M, et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection[J]. Gastroenterology, 2015, 148(1):126-136.e6. DOI:10.1053/j.gastro.2014.09.042 .
32	NADAULD L D, GARCIA S, NATSOULIS G, et al. Metastatic tumor evolution and organoid modeling implicate TGFBR2as a cancer driver in diffuse gastric cancer[J]. Genome Biol, 2014, 15(8):1-18. DOI:10.1186/s13059-014-0428-9 .
33	GRAHAM D Y. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits[J]. Gastroenterology, 2015, 148(4):719-31.e3. DOI:10.1053/j.gastro.2015.01.040 .
34	BURKITT M D, DUCKWORTH C A, WILLIAMS J M, et al. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models[J]. Dis Model Mech, 2017, 10(2):89-104. DOI:10.1242/dmm.027649 .
35	ÖHLUND D, HANDLY-SANTANA A, BIFFI G, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer[J]. J Exp Med, 2017, 214(3):579-596. DOI:10.1084/jem.20162024 .
36	SCHLAERMANN P, TOELLE B, BERGER H, et al. A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro [J]. Gut, 2016, 65(2):202-213. DOI:10.1136/gutjnl-2014-307949 .
37	SCANU T, SPAAPEN R M, BAKKER J M, et al. Salmonella manipulation of host signaling pathways provokes cellular transformation associated with gallbladder carcinoma[J]. Cell Host Microbe, 2015, 17(6):763-774. DOI:10.1016/j.chom. 2015. 05.002 .
38	MCCRACKEN K W, CATÁ E M, CRAWFORD C M, et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids[J]. Nature, 2014, 516(7531):400-404. DOI:10.1038/nature13863 .
39	SCHUMACHER M A, FENG R, AIHARA E, et al. Helicobacter pylori-induced sonic hedgehog expression is regulated by NFκB pathway activation: the use of a novel in vitro model to study epithelial response to infection[J]. Helicobacter, 2015, 20(1):19-28. DOI:10.1111/hel.12152 .
40	WEEBER F, OOFT S N, DIJKSTRA K K, et al. Tumor organoids as a pre-clinical cancer model for drug discovery[J]. Cell Chem Biol, 2017, 24(9):1092-1100. DOI:10.1016/j.chembiol. 2017.06.012 .
41	FRANCIES H E, BARTHORPE A, MCLAREN-DOUGLAS A, et al. Drug sensitivity assays of human cancer organoid cultures[J]. Methods Mol Biol, 2019, 1576:339-351. DOI:10.1007/7651_2016_10 .
42	ABERLE M R, BURKHART R A, TIRIAC H, et al. Patient-derived organoid models help define personalized management of gastrointestinal cancer[J]. Br J Surg, 2018, 105(2):e48-e60. DOI:10.1002/bjs.10726 .
43	DROST J, CLEVERS H. Organoids in cancer research[J]. Nat Rev Cancer, 2018, 18(7):407-418. DOI:10.1038/s41568-018-0007-6 .
44	HAAG G M. OPPOSITE: Outcome prediction of systemic treatment in esophagogastric carcinoma (OPPOSITE)[EB/OL]. [2019-02-18]. .
45	WALLASCHEK N, REUTER S, SILKENAT S, et al. Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids[J]. PLoS Pathog, 2021, 17(2): e1009210. DOI:10.1371/journal.ppat.1009210 .

特点 Characteristic	CL	CDX	PDX	GEMM	PDO
周期 Period	+++	++	++	+	+++
基因编辑 Genome editing	+++	+++	-	+++	+++
高通量筛选 High throughput screening	+++	-	-	-	+++
价格 Price	+++	++	++	+	++
临床相关性 Clinical interrelation	-	++	+++	++	+++
肿瘤微环境 Tumor microenvironment	-	++	++	+++	+
个性化治疗 Individualized treatment	-	+	++	+	+++

特点 Characteristic	CL	CDX	PDX	GEMM	PDO
周期 Period	+++	++	++	+	+++
基因编辑 Genome editing	+++	+++	-	+++	+++
高通量筛选 High throughput screening	+++	-	-	-	+++
价格 Price	+++	++	++	+	++
临床相关性 Clinical interrelation	-	++	+++	++	+++
肿瘤微环境 Tumor microenvironment	-	++	++	+++	+
个性化治疗 Individualized treatment	-	+	++	+	+++

[1]	Yinghan WAN, Yexin GU, Yunong YUAN, Min TANG, Li LU. Implications on the Development of Animal Disease Models from FDA Modernization Act 2.0 [J]. Laboratory Animal and Comparative Medicine, 2023, 43(5): 472-481.
[2]	SONG Weijie, ZHOU Yan, NIU Ruifang. Application of Laboratory Animal Models in Cancer Precision Medicine Research [J]. Laboratory Animal and Comparative Medicine, 2021, 41(6): 493-500.
[3]	ZHAO Guoping. Development Trend and Challenge of Comparative Medicine from Human Genome Project to Precision Medicine [J]. Laboratory Animal and Comparative Medicine, 2021, 41(1): 1-8.
[4]	LUO Baohua, ZHANG Yongbin, LIU Xiaoqiu, SHI Changhong. Establishment and Applications of Tumor Organoid Models [J]. Laboratory Animal and Comparative Medicine, 2020, 40(6): 540-546.
[5]	GE Xiao-mei, ZHANG Yi-xin, XIE Fu-bo, LIU Ji-bin, YANG Lei, QU Ying-ying, GU Ying, Li Xue-ting, YANG Wei-min, LIU Xi-peng, ZHOU He, QIANG Fu-lin. Establishment and Characterization of Patient Derived Gastric Cancer Cell Lines [J]. Laboratory Animal and Comparative Medicine, 2017, 37(4): 257-265.
[6]	CHU Fang, LI Yu-yun, FEI Jian, LI Yan-shu. Effect of Extractive from Glaucescent Fissistigma Root on Inhibiting Human Gastric Cancer and Ovarian Cancer in Nude Mice [J]. Laboratory Animal and Comparative Medicine, 2015, 35(1): 23-26.
[7]	XU Chun-hua, YANG Lei, TANG Xu-zhen, HU Gang, GENG Qin, OU YANG Ke-dong, XIE Fu-bo, WANG Ke, QIN Xiao-ran, LIU Ji-bin, YANG Wei-min, TAO Wei-kang, ZHANG Yi-xin, ZHOU He. Initially Establishment and Characterization of Patient Derived Gastric Cancer Xenograft Models [J]. Laboratory Animal and Comparative Medicine, 2014, 34(4): 259-265.
[8]	PENG Xiu-Hua, SHEN Yan, XU Chun-Hua, YANG Yu-Qin, ZHOU Wen-Jiang. Dynamic Observation On Growth of Subcutaneous and Orthotopic Gastric Tumor by in vivo Fluorescence Imager [J]. Laboratory Animal and Comparative Medicine, 2011, 31(5): 371-375.
[9]	WANG Si-feng, WANG Xi-mm，HOU Hai-rong, LIU Ke-chun, HAN Li-wen, CHEN Xi-qiang, WANG Xue. Selection of Organic Cosolvents in Experiment with Zebrafish [J]. , 2008, 28(4): 238-242.
[10]	CHEN Yu-Qiang, CHEN Fu, CHEN Zheng-Ming, WU Qiao, SU Wen-Jin. Effects of All-trans Retinoic Acid Treatment of Gastric Cancer Cells in Vitro on Their Growth in Nude Mouse Xenografts [J]. , 1998, 18(2): 81-84.