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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Review Article

Tumor Organoid as a Drug Screening Platform for Cancer Research

Author(s): Reyhaneh Mahbubi Arani, Niloufar Yousefi, Amir Ali Hamidieh, Fatemeh Gholizadeh and Mahsa Mollapour Sisakht*

Volume 19, Issue 9, 2024

Published on: 06 October, 2023

Page: [1210 - 1250] Pages: 41

DOI: 10.2174/011574888X268366230922080423

Price: $65

Abstract

A number of studies have been conducted on the application of 3D models for drug discovery, drug sensitivity assessment, and drug toxicity. Most of these studies focused on disease modelling and attempted to control cellular differentiation, heterogeneity, and key physiological features to mimic organ reconstitution so that researchers could achieve an accurate response in drug evaluation. Recently, organoids have been used by various scientists due to their highly organotypic structure, which facilitates the translation from basic research to the clinic, especially in cancer research. With this tool, researchers can perform high-throughput analyses of compounds and determine the exact effect on patients based on their genetic variations, as well as develop personalized and combination therapies. Although there is a lack of standardization in organoid culture, patientderived organoids (PDOs) have become widely established and used for drug testing. In this review, we have discussed recent advances in the application of organoids and tumoroids not only in cancer research for drug screening but also in clinical trials to demonstrate the potential of organoids in translational medicine.

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[1]
Tatullo M, Marrelli B, Benincasa C, et al. Organoids in translational oncology. J Clin Med 2020; 9(9): 2774.
[http://dx.doi.org/10.3390/jcm9092774] [PMID: 32867142]
[2]
Tortorella I, Argentati C, Emiliani C, Martino S, Morena F. The role of physical cues in the development of stem cell-derived organoids. Eur Biophys J 2021; 1-13.
[PMID: 34120215]
[3]
Zhao Z, Chen X, Dowbaj AM, et al. Organoids. Nature Reviews Methods Primers 2022; 2(1): 94.
[http://dx.doi.org/10.1038/s43586-022-00174-y] [PMID: 37325195]
[4]
Baldassari S, Musante I, Iacomino M, Zara F, Salpietro V, Scudieri P. Brain organoids as model systems for genetic neurodevelopmental disorders. Front Cell Dev Biol 2020; 8: 590119.
[http://dx.doi.org/10.3389/fcell.2020.590119] [PMID: 33154971]
[5]
Roux W. Beiträge zur entwickelungsmechanik des embryo. Virchows Arch 1888; 114(2): 246-91.
[http://dx.doi.org/10.1007/BF01882630]
[6]
Kim S, Choung S, Sun RX, et al. Comparison of cell and organoid-level analysis of patient-derived 3D organoids to evaluate tumor cell growth dynamics and drug response. SLAS Discov 2020; 25(7): 744-54.
[http://dx.doi.org/10.1177/2472555220915827] [PMID: 32349587]
[7]
Skardal A, Mack D, Atala A, Soker S. Substrate elasticity controls cell proliferation, surface marker expression and motile phenotype in amniotic fluid-derived stem cells. J Mech Behav Biomed Mater 2013; 17: 307-16.
[http://dx.doi.org/10.1016/j.jmbbm.2012.10.001] [PMID: 23122714]
[8]
Bruun J, Kryeziu K, Eide PW, et al. Patient-derived organoids from multiple colorectal cancer liver metastases reveal moderate intra-patient pharmacotranscriptomic heterogeneity. Clin Cancer Res 2020; 26(15): 4107-19.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-3637] [PMID: 32299813]
[9]
Riedl A, Schlederer M, Pudelko K, et al. Comparison of cancer cells in 2D vs 3D culture reveals differences in AKT-mTOR-S6K signaling and drug responses. J Cell Sci 2017; 130(1): 203-18.
[PMID: 27663511]
[10]
Sudhakaran M, Parra MR, Stoub H, Gallo KA, Doseff AI. Apigenin by targeting hnRNPA2 sensitizes triple-negative breast cancer spheroids to doxorubicin-induced apoptosis and regulates expression of ABCC4 and ABCG2 drug efflux transporters. Biochem Pharmacol 2020; 182: 114259.
[http://dx.doi.org/10.1016/j.bcp.2020.114259] [PMID: 33011162]
[11]
Zhang L, Liu F, Weygant N, et al. A novel integrated system using patient-derived glioma cerebral organoids and xenografts for disease modeling and drug screening. Cancer Lett 2021; 500: 87-97.
[http://dx.doi.org/10.1016/j.canlet.2020.12.013] [PMID: 33309780]
[12]
Onozato D, Akagawa T, Kida Y, et al. Application of human induced pluripotent stem cell-derived intestinal organoids as a model of epithelial damage and fibrosis in inflammatory bowel disease. Biol Pharm Bull 2020; 43(7): 1088-95.
[http://dx.doi.org/10.1248/bpb.b20-00088] [PMID: 32612071]
[13]
de Witte CJ, Espejo Valle-Inclan J, Hami N, et al. Patient-derived ovarian cancer organoids mimic clinical response and exhibit heterogeneous inter-and intrapatient drug responses. Cell Rep 2020; 31(11): 107762.
[http://dx.doi.org/10.1016/j.celrep.2020.107762] [PMID: 32553164]
[14]
Harrison RG. Observations on the living developing nerve fiber. Exp Biol Med 1906; 4(1): 140-3.
[http://dx.doi.org/10.3181/00379727-4-98]
[15]
Luca AC, Mersch S, Deenen R, et al. Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines. PLoS One 2013; 8(3): e59689.
[http://dx.doi.org/10.1371/journal.pone.0059689] [PMID: 23555746]
[16]
Shen FH, Werner BC, Liang H, et al. Implications of adipose-derived stromal cells in a 3D culture system for osteogenic differentiation: An in vitro and in vivo investigation. Spine J 2013; 13(1): 32-43.
[http://dx.doi.org/10.1016/j.spinee.2013.01.002] [PMID: 23384881]
[17]
Edmondson R, Broglie JJ, Adcock AF, Yang L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol 2014; 12(4): 207-18.
[http://dx.doi.org/10.1089/adt.2014.573] [PMID: 24831787]
[18]
Park Y, Huh KM, Kang SW. Applications of biomaterials in 3D cell culture and contributions of 3D cell culture to drug development and basic biomedical research. Int J Mol Sci 2021; 22(5): 2491.
[http://dx.doi.org/10.3390/ijms22052491] [PMID: 33801273]
[19]
Bassi G, Panseri S, Dozio SM, et al. Scaffold-based 3D cellular models mimicking the heterogeneity of osteosarcoma stem cell niche. Sci Rep 2020; 10(1): 22294.
[http://dx.doi.org/10.1038/s41598-020-79448-y] [PMID: 33339857]
[20]
Pompili L, Porru M, Caruso C, Biroccio A, Leonetti C. Patient-derived xenografts: A relevant preclinical model for drug development. J Exp Clin Cancer Res 2016; 35(1): 189.
[http://dx.doi.org/10.1186/s13046-016-0462-4] [PMID: 27919280]
[21]
Mehta G, Hsiao AY, Ingram M, Luker GD, Takayama S. Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J Control Release 2012; 164(2): 192-204.
[http://dx.doi.org/10.1016/j.jconrel.2012.04.045] [PMID: 22613880]
[22]
Li X, Pan B, Song X, et al. Breast cancer organoids from a patient with giant papillary carcinoma as a high-fidelity model. Cancer Cell Int 2020; 20(1): 86.
[http://dx.doi.org/10.1186/s12935-020-01171-5] [PMID: 32206037]
[23]
Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009; 459(7244): 262-5.
[http://dx.doi.org/10.1038/nature07935] [PMID: 19329995]
[24]
Shankaran A, Prasad K, Chaudhari S, Brand A, Satyamoorthy K. Advances in development and application of human organoids. 3 Biotech 2021; 11(6): 257.
[25]
Tricinci O, De Pasquale D, Marino A, Battaglini M, Pucci C, Ciofani G. A 3D biohybrid real‐scale model of the brain cancer microenvironment for advanced in vitro testing. Adv Mater Technol 2020; 5(10): 2000540.
[http://dx.doi.org/10.1002/admt.202000540] [PMID: 33088902]
[26]
Clevers H. Modeling development and disease with organoids. Cell 2016; 165(7): 1586-97.
[http://dx.doi.org/10.1016/j.cell.2016.05.082] [PMID: 27315476]
[27]
Lo YH, Kolahi KS, Du Y, et al. A CRISPR/Cas9-engineered ARID1A-deficient human gastric cancer organoid model reveals essential and nonessential modes of oncogenic transformation. Cancer Discov 2021; 11(6): 1562-81.
[http://dx.doi.org/10.1158/2159-8290.CD-20-1109] [PMID: 33451982]
[28]
Xu H, Jiao D, Liu A, Wu K. Tumor organoids: Applications in cancer modeling and potentials in precision medicine. J Hematol Oncol 2022; 15(1): 58.
[http://dx.doi.org/10.1186/s13045-022-01278-4] [PMID: 35551634]
[29]
Lee SH, Hu W, Matulay JT, Silva MV, Owczarek TB, Kim K. Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 2018; 173(2): 515-28.
[http://dx.doi.org/10.1016/j.cell.2018.03.017]
[30]
Huang L, Holtzinger A, Jagan I, et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell– and patient-derived tumor organoids. Nat Med 2015; 21(11): 1364-71.
[http://dx.doi.org/10.1038/nm.3973] [PMID: 26501191]
[31]
Sereti E, Papapostolou I, Dimas K. Pancreatic cancer organoids: An emerging platform for precision medicine? Biomedicines 2023; 11(3): 890.
[http://dx.doi.org/10.3390/biomedicines11030890] [PMID: 36979869]
[32]
Jensen LH, Rogatto SR, Lindebjerg J, et al. Precision medicine applied to metastatic colorectal cancer using tumor-derived organoids and in vitro sensitivity testing: A phase 2, single-center, open-label, and non-comparative study. J Exp Clin Cancer Res 2023; 42(1): 115.
[http://dx.doi.org/10.1186/s13046-023-02683-4] [PMID: 37143108]
[33]
Available From:https://clinicaltrials.gov/ct2/show/NCT03251612
[34]
Calandrini C, Schutgens F, Oka R, et al. An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity. Nat Commun 2020; 11(1): 1310.
[http://dx.doi.org/10.1038/s41467-020-15155-6] [PMID: 32161258]
[35]
Li Z, Qian Y, Li W, et al. Human lung adenocarcinoma-derived organoid models for drug screening. iScience 2020; 23(8): 101411.
[http://dx.doi.org/10.1016/j.isci.2020.101411] [PMID: 32771979]
[36]
Kim M, Mun H, Sung CO, et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat Commun 2019; 10(1): 3991.
[http://dx.doi.org/10.1038/s41467-019-11867-6] [PMID: 31488816]
[37]
Tindle C, Katkar GD, Fonseca AG, Taheri S, Lee J, Maity P. A living organoid biobank of crohn’s disease patients reveals molecular subtypes for personalized therapeutics. bioRxiv 2023.
[http://dx.doi.org/10.1101/2023.03.11.532245]
[38]
Xie X, Li X, Song W. Tumor organoid biobank-new platform for medical research. Sci Rep 2023; 13(1): 1819.
[http://dx.doi.org/10.1038/s41598-023-29065-2] [PMID: 36725963]
[39]
Botti G, Di Bonito M, Cantile M. Organoid biobanks as a new tool for pre-clinical validation of candidate drug efficacy and safety. Int J Physiol Pathophysiol Pharmacol 2021; 13(1): 17-21.
[PMID: 33815668]
[40]
Vernon M, Lambert B, Meryet-Figuière M, et al. Functional miRNA screening identifies wide-ranging antitumor properties of miR-3622b-5p and reveals a new therapeutic combination strategy in ovarian tumor organoids. Mol Cancer Ther 2020; 19(7): 1506-19.
[http://dx.doi.org/10.1158/1535-7163.MCT-19-0510] [PMID: 32371581]
[41]
Cho YH, Ro EJ, Yoon JS, et al. 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation. Nat Commun 2020; 11(1): 5321.
[http://dx.doi.org/10.1038/s41467-020-19173-2] [PMID: 33087710]
[42]
Lampart FL, Iber D, Doumpas N. Organoids in high-throughput and high-content screenings. Fron Chem Engineer 2023; 5: 1120348.
[http://dx.doi.org/10.3389/fceng.2023.1120348]
[43]
Schuster B, Junkin M, Kashaf SS, et al. Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids. Nat Commun 2020; 11(1): 5271.
[http://dx.doi.org/10.1038/s41467-020-19058-4] [PMID: 33077832]
[44]
Forsythe S, Mehta N, Devarasetty M, et al. Development of a colorectal cancer 3D micro-tumor construct platform from cell lines and patient tumor biospecimens for standard-of-care and experimental drug screening. Ann Biomed Eng 2020; 48(3): 940-52.
[http://dx.doi.org/10.1007/s10439-019-02269-2] [PMID: 31020445]
[45]
Zhu Y, Zhang X, Sun L, Wang Y, Zhao Y. Engineering human brain assembloids by microfluidics. Adv Mater 2023; 35(14): 2210083.
[http://dx.doi.org/10.1002/adma.202210083] [PMID: 36634089]
[46]
Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 2018; 359(6378): 920-6.
[http://dx.doi.org/10.1126/science.aao2774] [PMID: 29472484]
[47]
Christin JR, Shen MM. Modeling tumor plasticity in organoid models of human cancer. Trends Cancer 2022; 8(3): 161-3.
[http://dx.doi.org/10.1016/j.trecan.2021.12.004] [PMID: 35000880]
[48]
Yuan J, Li X, Yu S. Cancer organoid co-culture model system: Novel approach to guide precision medicine. Front Immunol 2023; 13: 1061388.
[http://dx.doi.org/10.3389/fimmu.2022.1061388] [PMID: 36713421]
[49]
Luo X, Wang J, Han Z, Yu Y, Chen Z, Huang F. Artificial intelligence− enhanced white-light colonoscopy with attention guidance predicts colorectal cancer invasion depth. Gastrointestinal Endoscopy 2021; 94(3): 627-38.
[50]
Goldrick C, Guri I, Herrera-Oropeza G, et al. 3D multicellular systems in disease modelling: From organoids to organ-on-chip. Front Cell Dev Biol 2023; 11: 1083175.
[http://dx.doi.org/10.3389/fcell.2023.1083175] [PMID: 36819106]
[51]
Frappart PO, Walter K, Gout J, et al. Pancreatic cancer‐derived organoids: A disease modeling tool to predict drug response. United European Gastroenterol J 2020; 8(5): 594-606.
[http://dx.doi.org/10.1177/2050640620905183] [PMID: 32213029]
[52]
Sekine K. Human organoid and supporting technologies for cancer and toxicological research. Front Genet 2021; 12: 759366.
[http://dx.doi.org/10.3389/fgene.2021.759366] [PMID: 34745227]
[53]
Bitler BG, Wu S, Park PH, et al. ARID1A-mutated ovarian cancers depend on HDAC6 activity. Nat Cell Biol 2017; 19(8): 962-73.
[http://dx.doi.org/10.1038/ncb3582] [PMID: 28737768]
[54]
Fukumoto T, Park PH, Wu S, et al. Repurposing Pan-HDAC inhibitors for ARID1A-mutated ovarian cancer. Cell Rep 2018; 22(13): 3393-400.
[http://dx.doi.org/10.1016/j.celrep.2018.03.019] [PMID: 29590609]
[55]
Shimizu T, Mae SI, Araoka T, et al. A novel ADPKD model using kidney organoids derived from disease-specific human iPSCs. Biochem Biophys Res Commun 2020; 529(4): 1186-94.
[http://dx.doi.org/10.1016/j.bbrc.2020.06.141] [PMID: 32819584]
[56]
Vijftigschild LAW, Berkers G, Dekkers JF, et al. β 2 -Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis. Eur Respir J 2016; 48(3): 768-79.
[http://dx.doi.org/10.1183/13993003.01661-2015] [PMID: 27471203]
[57]
Ha J, Kang JS, Lee M, et al. Simplified brain organoids for rapid and robust modeling of brain disease. Front Cell Dev Biol 2020; 8: 594090.
[http://dx.doi.org/10.3389/fcell.2020.594090] [PMID: 33195269]
[58]
Renner H, Grabos M, Becker KJ, et al. A fully automated high-throughput workflow for 3D-based chemical screening in human midbrain organoids. eLife 2020; 9: e52904.
[http://dx.doi.org/10.7554/eLife.52904] [PMID: 33138918]
[59]
Available From:https://www.medgadget.com/2021/03/new-models-in-organoids-market-open-new-vistas-in-stem-cell-research-for-cancer-global-valuation-to-reach-us-134-mn-by-2029-fmi.html
[60]
Takebe T, Wells JM, Helmrath MA, Zorn AM. Organoid center strategies for accelerating clinical translation. Cell Stem Cell 2018; 22(6): 806-9.
[http://dx.doi.org/10.1016/j.stem.2018.05.008] [PMID: 29859171]
[61]
Available From:https://www.researchnester.com/reports/organoids-market/2154
[62]
Available From:https://www.futuremarketinsights.com/reports/organoids-market
[63]
Ma Q, Tao H, Li Q, et al. OrganoidDB: A comprehensive organoid database for the multi-perspective exploration of bulk and single-cell transcriptomic profiles of organoids. Nucleic Acids Res 2023; 51(D1): D1086-93.
[http://dx.doi.org/10.1093/nar/gkac942] [PMID: 36271792]
[64]
Lee MO, Lee S, Jung CR, et al. Development of a quantitative prediction algorithm for target organ-specific similarity of human pluripotent stem cell-derived organoids and cells. Nat Commun 2021; 12(1): 4492.
[http://dx.doi.org/10.1038/s41467-021-24746-w] [PMID: 34301945]

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