Preclinical translational research and application of tumor organoids

doi:10.16352/j.issn.1001-6325.2024.09.1214

Abstract

Abstract: More and more in-depth tumor mechanism research and clinical precision treatment have put forward higher requirements for the technology for the establishment of tumor models.More and more tumor organoids have been applied. This model is able to reproduce the genomic, transcriptome, proteome and other omics features of parental tumors without heterogeneity found in cell line models. Based on these characteristics, tumor organoids have gradually become a representative preclinical model, facilitating the translation of new research results and precision treatment of patients. This article summarizes the latest progress of tumor organoids on R&D of technology and application, focusing on the current methods of establishing tumor organoids, opportunities and challenges in clinical and research application.

Key words: tumor organoid, precise treatment, organoid biobank

CLC Number:

R318.19

XIA Yujia, YANG Zhenli, LIU Yuqin. Preclinical translational research and application of tumor organoids[J]. Basic & Clinical Medicine, 2024, 44(9): 1214-1218.

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]	Hendriks D, Brouwers JF, Hamer K, et al. Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis[J]. Nat Biotechnol, 2023,41:1567-1581.
[3]	Sachs N, Ligt J D, Kopper O, et al. A living biobank of breast cancer organoids captures disease heterogeneity[J]. Cell, 2018, 172:373. doi: 10.1016/j.cell.2017.11.010.
[4]	Driehuis E, Kretzschmar K, Clevers H. Establishment of patient-derived cancer organoids for drug-screening applications[J]. Nat Protoc, 2020,15:3380-3409.
[5]	Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single lgr5+ liver stem cells induced by Wnt-driven regeneration[J]. Nature, 2013,494:247-250.
[6]	Kim S, Min S, Choi YS,et al. Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids[J]. Nat Commun, 2022,13:1692. doi: 10.1038/s41467-022-29279-4.
[7]	Smyth EC, Vlachogiannis G, Hedayat S, et al. EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers[J]. Gut,2021,70:1632-1641.
[8]	Liu J, MacNaughtan J, Kerbert AJC, et al. Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis[J]. Gut,2024,73:1183-1198.
[9]	Liu M, Zhang C, Gong X, et al. Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo[J]. Cell Stem Cell,2024,31:52-70.
[10]	Li Y, Tang S, Shi X, et al. Metabolic classification suggests the GLUT1/ALDOB/G6PD axis as a therapeutic target in chemotherapy-resistant pancreatic cancer[J]. Cell Rep Med,2023,4:101162. doi: 10.1016/j.xcrm.2023.101162.
[11]	Bi G, Zhang X, Li W, et al. Modeling alcohol-associated liver disease in humans using adipose stromal or stem cell-derived organoids[J]. Cell Rep Methods,2024,4:100778. doi: 10.1016/j.crmeth.2024.100778.
[12]	Braakhuis HM, Gremmer ER, Bannuscher A, et al. Transferability and reproducibility of exposed air-liquid interface co-culture lung models[J]. NanoImpact,2023,31:100466. doi: 10.1016/j.impact.2023.100466.
[13]	Park DS, Kozaki T, Tiwari SK, et al. IPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer[J]. Nature,2023,623:397-405.
[14]	Dayton TL, Alcala N, Moonen L, et al. Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites[J]. Cancer Cell,2023,41:2083-2099.
[15]	Zhao H, Cheng Y, Kalra A, et al. Generation and multiomic profiling of a TP53/CDKN2A double-knock-out gastroesophageal junction organoid model[J]. Sci Transl Med,2022,14:eabq6146. doi: 10.1126/scitranslmed.abq6146.
[16]	Guillen KP, Fujita M, Butterfield AJ, et al. A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology[J]. Nat Cancer,2022,3:232-250.
[17]	Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers[J]. Science, 2018,359:920-926.
[18]	Zhou Z, Van der Jeught K, Fang Y, et al. An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity[J]. Nat Biomed En,2021,5:1320-1335.
[19]	Lv T, Shen L, Xu X, et al. Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer[J]. Int J Cancer,2023,152:524-535.
[20]	Chen P, Zhang X, Ding R, et al. Patient-derived organoids can guide personalized-therapies for patients with advanced breast cancer[J]. Adv Sci (Weinh),2021,8:e2101176. doi: 10.1002/advs.202101176.
[21]	Farin HF, Mosa MH, Ndreshkjana B, et al. Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses[J]. Cancer Discov,2023,13:2192-2211.
[22]	Ahn Y, An JH, Yang HJ, et al. Human blood vessel organoids penetrate human cerebral organoids and form a vessel-like system[J]. Cells,2021,10:2036. doi: 10.3390/cells10082036.
[23]	Li Y, Liu S, Zhou K, et al. Neuromedin U programs eosinophils to promote mucosal immunity of the small intestine[J]. Science,2023,381:1189-1196.
[24]	Hu Y, Sui X, Song F, et al. Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week[J]. Nat Commun,2021,12:2581. doi: 10.1038/s41467-021-22676-1.
[25]	González-Callejo P, Vázquez-Aristizabal P, García-Astrain C, et al. 3D bioprinted breast tumor-stroma models for pre-clinical drug testing[J]. Mater Today Bio,2023,23:100826. doi: 10.1016/j.mtbio.2023.100826.