Progress of gastric cancer organoids in basic research and clinical application

doi:10.16352/j.issn.1001-6325.2024.09.1219

Abstract

Abstract: Gastric cancer ranks fifth in global cancer mortality, which is highly aggressive and heterogeneous. However, the research and treatment of gastric cancer is hindered by short of research models that may characterize the developmental properties of gastric cancer. Gastric cancer organoid is a multicellular three-dimensional structure developed in vitro, which can mimic the structure and function of native gastric cancer. Gastric cancer organoids have great application potential and development prospects in establishing gastric cancer research models, mimicking the tumor microenvironment, high-throughput screening of drugs, discovering new therapeutic targets, predicting clinical therapeutic responses, and guiding individualized treatment. In this paper, the progress of gastric cancer organoids in basic research and clinical application is reviewed aiming for promoting the progress of preclinical research and supporting the clinical treatment of gastric cancer.

Key words: gastric cancer, clinical treatment, organoid, tumor microenvironment

CLC Number:

R735.2

LIU Baoqing, HUANG Rong, LU Yan, LI Kai, ZHANG Ning, LIU Changzheng, SONG Wei. Progress of gastric cancer organoids in basic research and clinical application[J]. Basic & Clinical Medicine, 2024, 44(9): 1219-1222.

References 25

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024,74:229-263.
[2]	郑荣寿, 陈茹, 韩冰峰, 等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2024, 46: 221-231.
[3]	Thrift AP, Wenker TN, El-Serag HB. Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention[J]. Nat Rev Clin Oncol, 2023,20:338-349.
[4]	Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up[J]. Ann Oncol, 2022,33:1005-1020.
[5]	Sato T, Vries R G, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche[J]. Nature, 2009,459:262-265.
[6]	LeSavage BL, Suhar RA, Broguiere N, et al. Next-generation cancer organoids[J]. Nat Mater, 2022,21:143-159.
[7]	Marx V. Closing in on cancer heterogeneity with organoids[J]. Nat Methods, 2024,21:551-554.
[8]	Yan H, Chan AS, Lai FP, et al. Organoid cultures for cancer modeling[J]. Cell Stem Cell, 2023,30:917-937.
[9]	McCracken KW, Catá EM, Crawford CM, et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids[J]. Nature, 2014,516:400-404.
[10]	Huang XZ, Pang MJ, Li JY, et al. Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis[J]. Nat Commun, 2023,14:822. doi: 10.1038/s41467-023-36310-9.
[11]	Koh V, Chakrabarti J, Torvund M, et al. Hedgehog transcriptional effector GLI mediates mTOR-Induced PD-L1 expression in gastric cancer organoids[J]. Cancer Lett, 2021,518:59-71.
[12]	Yao L, Hou J, Wu X, et al. Cancer-associated fibroblasts impair the cytotoxic function of NK cells in gastric cancer by inducing ferroptosis via iron regulation[J]. Redox Biol, 2023,67:102923. doi:10.1016/j.redox.2023.102923.
[13]	Zhao H, Cheng Y, Kalra A, et al. Generation and multiomic profiling of a TP53/CDKN2A double-knoc-kout gastroesophageal junction organoid model[J]. Sci Transl Med, 2022,14:eabq6146. doi:10.1126/scitranslmed.abq6146.
[14]	Zhang F, Sahu V, Peng K, et al. Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer[J]. Gut, 2024:gutjnl-2023-329686. doi: 10.1136/gutjnl-2023-329686.
[15]	Arai J, Hayakawa Y, Tateno H, et al. Impaired glycosylation of gastric mucins drives gastric tumorigenesis and serves as a novel therapeutic target[J]. Gastroenterology, 2024. doi:10.1053/j.gastro.2024.03.037.
[16]	Mircetic J, Camgöz A, Abohawya M, et al. CRISPR/Cas9 screen in gastric cancer patient-derived organoids reveals KDM1A-NDRG1 axis as a targetable vulnerability[J]. Small Methods, 2023,7:e2201605. doi:10.1002/smtd.202201605.
[17]	Peng K, Zhang F, Wang Y, et al. Development of combination strategies for focal adhesion kinase inhibition in diffuse gastric cancer[J]. Clin Cancer Res, 2023,29:197-208.
[18]	Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers[J]. Science, 2018,359:920-926.
[19]	Zu M, Hao X, Ning J, et al. Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing[J]. Biomed Pharmacother, 2023,163:114751. doi:10.1016/j.biopha.2023.114751.
[20]	Schmäche T, Fohgrub J, Klimova A, et al. Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold[J]. Mol Cancer, 2024,23:10. doi:10.1186/s12943-023-01919-3.
[21]	Lin W, Zhang Y, Yang Y, et al. Anti-PD-1/Her2 bispecific antibody IBI315 enhances the treatment effect of Her2-positive gastric cancer through gasdermin B-cleavage induced pyroptosis[J]. Adv Sci (Weinh), 2023,10:e2303908. doi:10.1002/advs.202303908.
[22]	Kwon JW, Oh JS, Seok SH, et al. Combined inhibition of Bcl-2 family members and YAP induces synthetic lethality in metastatic gastric cancer with RASA1 and NF2 deficiency[J]. Mol Cancer, 2023,22:156. doi:10.1186/s12943-023-01857-0.
[23]	Dao L, You Z, Lu L, et al. Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids[J]. Cell Stem Cell, 2024,31:818-833.
[24]	Hwangbo H, Chae S, Kim W, et al. Tumor-on-a-chip models combined with mini-tissues or organoids for engineering tumor tissues[J]. Theranostics, 2024,14:33-55.
[25]	Wu J, Li T, Guo M, et al. Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue[J]. Cell Discov, 2024,10:45. doi:10.1038/s41421-024-00662-3.