Tumor Organoid as a Drug Screening Platform for Cancer Research

  • Authors: Arani R.1, Yousefi N.2, Hamidieh A.3, Gholizadeh F.4, Sisakht M.5
  • Affiliations:
    1. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Shahid Beheshti University of Medical Sciences
    2. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences
    3. Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences
    4. Stem Cell and Regenerative Medicine Center of Excellence, Tehran University of Medical Sciences
    5. Biotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences
  • Issue: Vol 19, No 9 (2024)
  • Pages: 1210-1250
  • Section: Medicine
  • URL: https://rjpbr.com/1574-888X/article/view/645927
  • DOI: https://doi.org/10.2174/011574888X268366230922080423
  • ID: 645927

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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.

About the authors

Reyhaneh Arani

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Shahid Beheshti University of Medical Sciences

Email: info@benthamscience.net

Niloufar Yousefi

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences

Email: info@benthamscience.net

Amir Hamidieh

Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences

Email: info@benthamscience.net

Fatemeh Gholizadeh

Stem Cell and Regenerative Medicine Center of Excellence, Tehran University of Medical Sciences

Email: info@benthamscience.net

Mahsa Sisakht

Biotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  1. Tatullo M, Marrelli B, Benincasa C, et al. Organoids in translational oncology. J Clin Med 2020; 9(9): 2774. doi: 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. doi: 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. doi: 10.3389/fcell.2020.590119 PMID: 33154971
  5. Roux W. Beiträge zur entwickelungsmechanik des embryo. Virchows Arch 1888; 114(2): 246-91. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1002/admt.202000540 PMID: 33088902
  26. Clevers H. Modeling development and disease with organoids. Cell 2016; 165(7): 1586-97. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1177/2050640620905183 PMID: 32213029
  52. Sekine K. Human organoid and supporting technologies for cancer and toxicological research. Front Genet 2021; 12: 759366. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1038/s41467-021-24746-w PMID: 34301945

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