Organoid thực quản: ứng dụng và triển vọng tương lai

Springer Science and Business Media LLC - Tập 101 - Trang 931-945 - 2023
Hongyuan Liu1, Xianli Wang2
1Shanghai Jiao Tong University School of Medicine, Shanghai, China
2Shanghai Jiao Tong University School of Public Health, Shanghai, China

Tóm tắt

Các organoid đã được phát triển trong thập kỷ qua như một công cụ nghiên cứu mới để mô phỏng sinh học tế bào của cơ quan và bệnh lý. So với các dòng tế bào 2D truyền thống và các mô hình động vật, dữ liệu thực nghiệm dựa trên organoid thực quản đáng tin cậy hơn. Trong những năm gần đây, các organoid thực quản được tạo ra từ nhiều nguồn tế bào đã được thiết lập, và các quy trình nuôi cấy tương đối trưởng thành đã được phát triển. Viêm thực quản và ung thư là hai hướng chính trong mô hình hóa organoid thực quản, và các mô hình organoid của ung thư biểu mô tuyến thực quản, ung thư biểu mô tế bào vảy thực quản, và viêm thực quản bạch cầu ái toan đã được thiết lập. Các đặc tính của organoid thực quản, mô phỏng thực quản thật, góp phần vào nghiên cứu trong sàng lọc thuốc và y học tái tạo. Việc kết hợp organoid với các công nghệ khác như chips cơ quan và tế bào xenograft có thể bổ sung cho những thiếu sót của organoid và tạo ra các mô hình nghiên cứu hoàn toàn mới có lợi hơn cho nghiên cứu ung thư. Trong bài đánh giá này, chúng tôi sẽ tóm tắt sự phát triển của các organoid ung thư và không ung thư thực quản, ứng dụng hiện tại của organoid thực quản trong mô hình hóa bệnh, y học tái tạo và sàng lọc thuốc. Chúng tôi cũng sẽ thảo luận về triển vọng tương lai của organoid thực quản.

Từ khóa

#organoid thực quản #viêm thực quản #ung thư thực quản #y học tái tạo #sàng lọc thuốc

Tài liệu tham khảo

Uhlenhopp DJ, Then EO, Sunkara T et al (2020) Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol 13(6):1010–1021. https://doi.org/10.1007/s12328-020-01237-x Peters Y, Al-Kaabi A, Shaheen NJ et al (2019) Barrett oesophagus Nat Rev Dis Primers 5(1):35. https://doi.org/10.1038/s41572-019-0086-z GBD (2017) Oesophageal Cancer Collaborators (2020) The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 5(6):582–597. https://doi.org/10.1016/S2468-1253(20)30007-8 Sawas T, Killcoyne S, Iyer PG et al (2018) Identification of prognostic phenotypes of esophageal adenocarcinoma in 2 independent cohorts. Gastroenterology 155(6):1720–1728.e4. https://doi.org/10.1053/j.gastro.2018.08.036 Molina-Infante J, Schoepfer AM, Lucendo AJ et al (2017) Eosinophilic esophagitis: what can we learn from Crohn’s disease? United European Gastroenterol J 5(6):762–772. https://doi.org/10.1177/2050640616672953 Ng SC, Shi HY, Hamidi N et al (2017) Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390(10114):2769–2778. https://doi.org/10.1016/S0140-6736(17)32448-0 Ishimura N, Okimoto E, Shibagaki K et al (2021) Similarity and difference in the characteristics of eosinophilic esophagitis between Western countries and Japan. Dig Endosc 33(5):708–719 Rossi G, Manfrin A, Lutolf MP (2018) Progress and potential in organoid research. Nat Rev Genet 19(11):671–687. https://doi.org/10.1038/s41576-018-0051-9 Sato T, Vries RG, Snippert HJ et al (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459(7244):262–265. https://doi.org/10.1038/nature07935 Nguyen R, Da Won BS, Qiao L et al (2021) Developing liver organoids from induced pluripotent stem cells (iPSCs): an alternative source of organoid generation for liver cancer research. Cancer Lett 508:13–17. https://doi.org/10.1016/j.canlet.2021.03.017 Zhu X, Zhang B, He Y et al (2021) Liver organoids: formation strategies and biomedical applications. Tissue Eng Regen Med 18(4):573–585. https://doi.org/10.1007/s13770-021-00357-w Hohwieler M, Illing A, Hermann PC et al (2017) Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut 66(3):473–486. https://doi.org/10.1136/gutjnl-2016-312423 Grenier K, Kao J, Diamandis P (2020) Three-dimensional modeling of human neurodegeneration: brain organoids coming of age. Mol Psychiatry 25(2):254–274. https://doi.org/10.1038/s41380-019-0500-7 Seidlitz T, Merker SR, Rothe A et al (2019) Human gastric cancer modelling using organoids. Gut 68(2):207–217. https://doi.org/10.1136/gutjnl-2017-314549 Quante M, Bhagat G, Abrams JA et al (2012) Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell 21(1):36–51. https://doi.org/10.1016/j.ccr.2011.12.004 Tang XH, Knudsen B, Bemis D et al (2004) Oral cavity and esophageal carcinogenesis modeled in carcinogen-treated mice. Clin Cancer Res 10(1 Pt 1):301–313. https://doi.org/10.1158/1078-0432.ccr-0999-3 Stairs DB, Bayne LJ, Rhoades B et al (2011) Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene. Cancer Cell 19(4):470–483. https://doi.org/10.1016/j.ccr.2011.02.007 Opitz OG, Harada H, Suliman Y et al (2002) A mouse model of human oral-esophageal cancer. J Clin Invest 110(6):761–769. https://doi.org/10.1172/JCI15324 Camilleri AE, Nag S, Russo AR et al (2021) Gene therapy for a murine model of eosinophilic esophagitis. Allergy 76(9):2740–2752. https://doi.org/10.1111/all.14822 Kawaura Y, Tatsuzawa Y, Wakabayashi T et al (2001) Immunohistochemical study of p53, c-erbB-2, and PCNA in Barrett’s esophagus with dysplasia and adenocarcinoma arising from experimental acid or alkaline reflux model. J Gastroenterol 36(9):595–600. https://doi.org/10.1007/s005350170042 Kadirkamanathan SS, Yazaki E, Evans DF et al (2001) An ambulant porcine model of acid reflux used to evaluate endoscopic gastroplasty. Gut 44(6):782–788. https://doi.org/10.1136/gut.44.6.782 Kapoor H, Lohani KR, Lee TH et al (2015) Animal models of Barrett’s esophagus and esophageal adenocarcinoma-past, present, and future. Clin Transl Sci 8(6):841–847. https://doi.org/10.1111/cts.12304 Kruger L, Gonzalez LM, Pridgen TA et al (2017) Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair. Am J Physiol Gastrointest Liver Physiol 313(3):G180–G191. https://doi.org/10.1152/ajpgi.00036.2017 Harada H, Nakagawa H, Oyama K et al (2003) Telomerase induces immortalization of human esophageal keratinocytes without p16INK4a inactivation. Mol Cancer Res 1(10):729–738 Harada H, Nakagawa H, Takaoka M et al (2008) Cleavage of MCM2 licensing protein fosters senescence in human keratinocytes. Cell Cycle 7(22):3534–3538. https://doi.org/10.4161/cc.7.22.7043 Ohashi S, Natsuizaka M, Wong GS et al (2010) Epidermal growth factor receptor and mutant p53 expand an esophageal cellular subpopulation capable of epithelial-to-mesenchymal transition through ZEB transcription factors. Cancer Res 70(10):4174–4184. https://doi.org/10.1158/0008-5472.CAN-09-4614 Ohashi S, Natsuizaka M, Yashiro-Ohtani Y et al (2010) NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL-dependent transcriptional network. Gastroenterology 139(6):2113–2123. https://doi.org/10.1053/j.gastro.2010.08.040 Whelan KA, Muir AB, Nakagawa H (2018) Esophageal 3D culture systems as modeling tools in esophageal epithelial pathobiology and personalized medicine. Cell Mol Gastroenterol Hepatol 5(4):461–478. https://doi.org/10.1016/j.jcmgh.2018.01.011 Yoshida GJ (2020) Applications of patient-derived tumor xenograft models and tumor organoids. J Hematol Oncol 13(1):4. https://doi.org/10.1186/s13045-019-0829-z Lan T, Xue X, Dunmall LC et al (2021) Patient-derived xenograft: a developing tool for screening biomarkers and potential therapeutic targets for human esophageal cancers. Aging 13(8):1227–12293. https://doi.org/10.18632/aging.202934 Dodbiba L, Teichman J, Fleet A et al (2013) Primary esophageal and gastro-esophageal junction cancer xenograft models: clinicopathological features and engraftment. Lab Invest 93(4):397–407. https://doi.org/10.1038/labinvest.2013.8 Dodbiba L, Teichman J, Fleet A et al (2015) Appropriateness of using patient-derived xenograft models for pharmacologic evaluation of novel therapies for esophageal/gastro-esophageal junction cancers. PLoS One 10(3):e0121872. https://doi.org/10.1371/journal.pone.0121872 Sanchez-Vega F, Hechtman JF, Castel P et al (2019) EGFR and MET amplifications determine response to HER2 inhibition in ERBB2-amplified esophagogastric cancer. Cancer Discov 9(2):199–209. https://doi.org/10.1158/2159-8290.CD-18-0598 Ebbing EA, van der Zalm AP, Steins A et al (2019) Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma. Proc Natl Acad Sci U S A 116(6):2237–2242. https://doi.org/10.1073/pnas.1820459116 Clevers H (2016) Modeling development and disease with organoids. Cell 165:1586–1597 Sachdeva UM, Shimonosono M, Flashner S et al (2021) Understanding the cellular origin and progression of esophageal cancer using esophageal organoids. Cancer Lett 509:39–52. https://doi.org/10.1016/j.canlet.2021.03.031 Zhang Y, Yang Y, Jiang M et al (2018) 3D Modeling of esophageal development using human PSC-derived basal progenitors reveals a critical role for Notch signaling. Cell Stem Cell 23(4):516–529.e5. https://doi.org/10.1016/j.stem.2018.08.009 Trisno SL, Philo KED, McCracken KW et al (2018) Esophageal organoids from human pluripotent stem cells delineate Sox2 functions during esophageal specification. Cell Stem Cell 23(4):501–515.e7. https://doi.org/10.1016/j.stem.2018.08.008 Schutgens F, Clevers H (2020) Human organoids: tools for understanding biology and treating diseases. Annu Rev Pathol 15:211–234. https://doi.org/10.1146/annurev-pathmechdis-012419-032611 Brassard JA, Lutolf MP (2019) Engineering stem cell self-organization to build better organoids. Cell Stem Cell 24:860–876. https://doi.org/10.1016/j.stem.2019.05.005 Tang XY, Wu S, Wang D et al (2022) Human organoids in basic research and clinical applications. Signal Transduct Target Ther 7(1):168. https://doi.org/10.1038/s41392-022-01024-9 Jiminez JA, Uwiera TC, Douglas Inglis G et al (2015) Animal models to study acute and chronic intestinal inflammation in mammals. Gut Pathog 7:29. https://doi.org/10.1186/s13099-015-0076-y Sasai Y (2013) Next-generation regenerative medicine: organogenesis from stem cells in 3D culture. Cell Stem Cell 12(5):520–530. https://doi.org/10.1016/j.stem.2013.04.009 He S, Hu B, Li C et al (2018) PDXliver: a database of liver cancer patient derived xenograft mouse models. BMC Cancer 18(1):550. https://doi.org/10.1186/s12885-018-4459-6 DeWard AD, Cramer J, Lagasse E (2014) Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep 9(2):701–711. https://doi.org/10.1016/j.celrep.2014.09.027 Kasagi Y, Chandramouleeswaran PM, Whelan KA et al (2018) The esophageal organoid system reveals functional interplay between notch and cytokines in reactive epithelial changes. Cell Mol Gastroenterol Hepatol 5(3):333–352. https://doi.org/10.1016/j.jcmgh.2017.12.013 Bailey DD, Zhang Y, van Soldt BJ et al (2019) Use of hPSC-derived 3D organoids and mouse genetics to define the roles of YAP in the development of the esophagus. Development 146(23):dev178855. https://doi.org/10.1242/dev.178855 Sato T, Stange DE, Ferrante M et al (2011) Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141(5):1762–1772. https://doi.org/10.1053/j.gastro.2011.07.050 Li X, Francies HE, Secrier M et al (2018) Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nat Commun 9(1):2983. https://doi.org/10.1038/s41467-018-05190-9 Kijima T, Nakagawa H, Shimonosono M et al (2018) Three-dimensional organoids reveal therapy resistance of esophageal and oropharyngeal squamous cell carcinoma cells. Cell Mol Gastroenterol Hepatol 7(1):73–91. https://doi.org/10.1016/j.jcmgh.2018.09.003 Karakasheva T A, Kijima T, Shimonosono M et al (2020) Generation and characterization of patient-derived head and neck, oral, and esophageal cancer organoids. Curr Protoc Stem Cell Biol 53(1):e109. https://doi.org/10.1002/cpsc.109 Zheng B, Ko KP, Fang X et al (2021) A new murine esophageal organoid culture method and organoid-based model of esophageal squamous cell neoplasia. IScience 24(12):103440. https://doi.org/10.1016/j.isci.2021.103440 Fan N, Raatz L, Chon SH et al (2022) Subculture and Cryopreservation of esophageal adenocarcinoma organoids: pros and cons for single cell digestion. J Vis Exp. https://doi.org/10.3791/63281 Giobbe GG, Crowley C, Luni C et al (2019) Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat Commun 10(1):5658. https://doi.org/10.1038/s41467-019-13605-4 Naranjo JD, Saldin LT, Sobieski E et al (2020) Esophageal extracellular matrix hydrogel mitigates metaplastic change in a dog model of Barrett’s esophagus. Sci Adv 6(27):eaba4526. https://doi.org/10.1126/sciadv.aba4526 Curvello R, Kerr G, Micati DJ et al (2020) Engineered plant-based nanocellulose hydrogel for small intestinal organoid growth. Adv Sci (Weinh) 8(1):2002135. https://doi.org/10.1002/advs.202002135 Sorrentino G, Rezakhani S, Yildiz E et al (2020) Mechano-modulatory synthetic niches for liver organoid derivation. Nat Commun 11(1):3416. https://doi.org/10.1038/s41467-020-17161-0 Thrift AP (2016) The epidemic of oesophageal carcinoma: where are we now? Cancer Epidemiol 41:88–95. https://doi.org/10.1016/j.canep.2016.01.013 Beydoun AS, Stabenau KA, Altman KW et al (2023) Cancer risk in Barrett’s esophagus: a clinical review. Int J Mol Sci 24(7):6018. https://doi.org/10.3390/ijms24076018 McDonald SAC, Lavery D, Wright NA et al (2015) Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol 12(1):50–60. https://doi.org/10.1038/nrgastro.2014.181 Kendall BJ, Whiteman DC (2006) Temporal changes in the endoscopic frequency of new cases of Barrett’s esophagus in an Australian health region. Am J Gastroenterol 101(6):1178–1182. https://doi.org/10.1111/j.1572-0241.2006.00548.x Spechler SJ, Souza RF (2014) Barrett’s esophagus. N Engl J Med 371(9):836–845. https://doi.org/10.1056/NEJMra1314704 Anaparthy R, Sharma P (2014) Progression of Barrett oesophagus: role of endoscopic and histological predictors. Nat Rev Gastroenterol Hepatol 11(9):525–534. https://doi.org/10.1038/nrgastro.2014.69 Liu X, Cheng Y, Abraham JM et al (2018) Modeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids. Cancer Lett 436:109–118. https://doi.org/10.1016/j.canlet.2018.08.017 Kunze B, Wein F, Fang HY et al (2020) Notch signaling mediates differentiation in Barrett’s esophagus and promotes progression to adenocarcinoma. Gastroenterology 159(2):575–590. https://doi.org/10.1053/j.gastro.2020.04.033 Anand A, Fang HY, Mohammad-Shahi D et al (2021) Elimination of NF-κB signaling in vimentin+ stromal cells attenuates tumorigenesis in a mouse model of Barrett’s esophagus. Carcinogenesis 42(3):405–413. https://doi.org/10.1093/carcin/bgaa109 Nakagawa H, Whelan K, Lynch JP (2015) Mechanisms of Barrett’s oesophagus: intestinal differentiation, stem cells, and tissue models. Best Pract Res Clin Gastroenterol 29(1):3–16. https://doi.org/10.1016/j.bpg.2014.11.001 Jiang M, Li H, Zhang Y et al (2017) Transitional basal cells at the squamous-columnar junction generate Barrett’s oesophagus. Nature 550(7677):529–533. https://doi.org/10.1038/nature24269 Nowicki-Osuch K, Zhuang L, Jammula S et al (2021) Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition. Science 373(6556):760–767. https://doi.org/10.1126/science.abd1449 Lee MH, Buterbaugh K, Richards-Kortum R et al (2012) Advanced endoscopic imaging for Barrett’s esophagus: current options and future directions. Curr Gastroenterol Rep 14(3):216–225. https://doi.org/10.1007/s11894-012-0259-3 Fang HY, Stangl S, Marcazzan S et al (2022) Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus. Eur J Nucl Med Mol Imaging 49(6):2049–2063. https://doi.org/10.1007/s00259-021-05582-y Sahm V, Maurer C, Baumeister T et al (2022) Telomere shortening accelerates tumor initiation in the L2-IL1B mouse model of Barrett esophagus and emerges as a possible biomarker. Oncotarget 13:347–359. https://doi.org/10.18632/oncotarget.28198 Lin Y, Totsuka Y, He Y et al (2013) Epidemiology of esophageal cancer in Japan and China. J Epidemiol 23(4):233–242. https://doi.org/10.2188/jea.je20120162 Liu K, Zhao T, Wang J et al (2019) Etiology, cancer stem cells and potential diagnostic biomarkers for esophageal cancer. Cancer Lett 458:21–28. https://doi.org/10.1016/j.canlet.2019.05.018 Hayakawa Y, Nakagawa H, Rustgi AK et al (2021) Stem cells and origins of cancer in the upper gastrointestinal tract. Cell Stem Cell 28(8):1343–1361. https://doi.org/10.1016/j.stem.2021.05.012 Natsuizaka M, Whelan KA, Kagawa S et al (2017) Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma. Nat Commun 8(1):1758. https://doi.org/10.1038/s41467-017-01500-9 Kajiwara C, Fumoto K, Kimura H et al (2018) p63-dependent Dickkopf3 expression promotes esophageal cancer cell proliferation via CKAP4. Cancer Res 78(21):6107–6120. https://doi.org/10.1158/0008-5472.CAN-18-1749 Tang Q, Lento A, Suzuki K et al (2021) Rab11-FIP1 mediates epithelial-mesenchymal transition and invasion in esophageal cancer. EMBO Rep 22(2):e48351. https://doi.org/10.15252/embr.201948351 Wu Z, Zhou J, Zhang X et al (2021) Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. Nat Genet 53(6):881–894. https://doi.org/10.1038/s41588-021-00859-2 Shimonosono M, Tanaka K, Flashner S et al (2021) Alcohol metabolism enriches squamous cell carcinoma cancer stem cells that survive oxidative stress via autophagy. Biomolecules 11(10):1479. https://doi.org/10.3390/biom11101479 Hruz P, Straumann A, Bussmann C et al (2011) Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol 128:1349–1350. https://doi.org/10.1016/j.jaci.2011.09.013 Attwood SE, Smyrk TC, Demeester TR et al (1993) Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 38(1):109–116. https://doi.org/10.1007/BF01296781 Dellon ES, Liacouras CA (2014) Advances in clinical management of eosinophilic esophagitis. Gastroenterology 147(6):1238–1254. https://doi.org/10.1053/j.gastro.2014.07.055 Muir A, Falk GW (2021) Eosinophilic esophagitis: a review. JAMA 326(13):1310–1318. https://doi.org/10.1001/jama.2021.14920 Navarro P, Arias Á, Arias-González L, Laserna-Mendieta EJ, Ruiz-Ponce M, Lucendo AJ (2019) Systematic review with meta-analysis: the growing incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther 49(9):1116–1125. https://doi.org/10.1111/apt.15231 Whelan KA, Merves JF, Giroux V et al (2017) Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. Gut 66(7):1197–1207. https://doi.org/10.1136/gutjnl-2015-310341 Nakagawa H, Kasagi Y, Karakasheva TA et al (2020) Modeling epithelial homeostasis and reactive epithelial changes in human and murine three-dimensional esophageal organoids. Curr Protoc Stem Cell Biol 52(1):e106. https://doi.org/10.1002/cpsc.106 Kaymak T, Kaya B, Wuggenig P et al (2022) IL-20 subfamily cytokines impair the oesophageal epithelial barrier by diminishing filaggrin in eosinophilic oesophagitis. Gut. https://doi.org/10.1136/gutjnl-2022-327166 Akdis CA (2021) Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol 21(11):739–751. https://doi.org/10.1038/s41577-021-00538-7 Doyle AD, Masuda MY, Pyon GC et al (2023) Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus. Allergy 78(1):192–201. https://doi.org/10.1111/all.15457 Hara T, Kasagi Y, Wang J et al (2022) CD73+ epithelial progenitor cells that contribute to homeostasis and renewal are depleted in eosinophilic esophagitis. Cell Mol Gastroenterol Hepatol 13(5):1449–1467. https://doi.org/10.1016/j.jcmgh.2022.01.018 van Lennep M, Singendonk MMJ, Dall’Oglio L et al (2019) Oesophageal atresia Nat Rev Dis Primers 5(1):26. https://doi.org/10.1038/s41572-019-0077-0 Spitz L, Kiely E, Pierro A (2004) Gastric transposition in children–a 21-year experience. J Pediatr Surg 39(3):276–281. https://doi.org/10.1016/j.jpedsurg.2003.11.032 Hamza AF, Abdelhay S, Sherif H et al (2003) Caustic esophageal strictures in children: 30 years’ experience. J Pediatr Surg 38(6):828–833. https://doi.org/10.1016/s0022-3468(03)00105-2 Bax NM, van der Zee DC (2007) Jejunal pedicle grafts for reconstruction of the esophagus in children. J Pediatr Surg 42(2):363–369. https://doi.org/10.1016/j.jpedsurg.2006.10.009 Spitz L (2007) Oesophageal atresia. Orphanet J Rare Dis 2:24. https://doi.org/10.1186/1750-1172-2-24 Low DE (2011) Update on staging and surgical treatment options for esophageal cancer. J Gastrointest Surg 15:719. https://doi.org/10.1007/s11605-011-1515-9 Spurrier RG, Speer AL, Hou X et al (2015) Murine and human tissue-engineered esophagus form from sufficient stem/progenitor cells and do not require microdesigned biomaterials. Tissue Eng Part A 21(5–6):906–915. https://doi.org/10.1089/ten.TEA.2014.0357 Trecartin A, Danopoulos S, Spurrier R et al (2016) Establishing proximal and distal regional identities in murine and human tissue-engineered lung and trachea. Tissue Eng Part C Methods 22(11):1049–1057. https://doi.org/10.1089/ten.TEC.2016.0261 Finkbeiner SR, Freeman JJ, Wieck MM et al (2015) Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids. Biol Open 4(11):1462–1472. https://doi.org/10.1242/bio.013235 Liu C, Qin T, Huang Y et al (2020) Drug screening model meets cancer organoid technology. Transl Oncol 13(11):100840. https://doi.org/10.1016/j.tranon.2020.100840 Baker EJ, Beck NA, Berg EL et al (2019) Advancing nonclinical innovation and safety in pharmaceutical testing. Drug Discov Today 24(2):624–628. https://doi.org/10.1016/j.drudis.2018.11.011 Caponigro G, Sellers WR (2011) Advances in the preclinical testing of cancer therapeutic hypotheses. Nat Rev Drug Discov 10(3):179–187. https://doi.org/10.1038/nrd3385 Derouet MF, Allen J, Wilson GW et al (2020) Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor. Sci Rep 10(1):14514. https://doi.org/10.1038/s41598-020-71589-4 Shapiro J, van Lanschot JJB, Hulshof MCCM et al (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16:1090–1098. https://doi.org/10.1016/S1470-2045(15)00040-6 Eyck BM, van Lanschot JJB, Hulshof MCCM et al (2021) 10-year outcome of a randomized trial comparing neoadjuvant chemoradiotherapy and surgery with surgery alone for esophageal cancer (CROSS trial). Eur J Surg Oncol 47:e31. https://doi.org/10.1200/JCO.20.03614 Dings MPG, van der Zalm AP, Bootsma S et al (2022) Estrogen-related receptor alpha drives mitochondrial biogenesis and resistance to neoadjuvant chemoradiation in esophageal cancer. Cell Rep Med 3(11):100802. https://doi.org/10.1016/j.xcrm.2022.100802 Driehuis E, Kolders S, Spelier S et al (2019) Oral mucosal organoids as a potential platform for personalized cancer therapy. Cancer Discov 9(7):852–871. https://doi.org/10.1158/2159-8290.CD-18-1522 Driehuis E, Kretzschmar K, Clevers H (2020) Establishment of patient-derived cancer organoids for drug-screening applications. Nat Protoc 15(10):3380–3409. https://doi.org/10.1038/s41596-020-0379-4 Karakasheva TA, Gabre JT, Sachdeva UM et al (2021) Patient-derived organoids as a platform for modeling a patient’s response to chemoradiotherapy in esophageal cancer. Sci Rep 11(1):21304. https://doi.org/10.1038/s41598-021-00706-8 Zhou Z, Cong L, Cong X (2021) Patient-derived organoids in precision medicine: drug screening, organoid-on-a-chip and living organoid biobank. Front Oncol 11:762184. Patient-Derived Organoids in Precision Medicine: Drug Screening, Organoid-on-a-Chip and Living Organoid Biobank Kawasaki K, Toshimitsu K, Matano M et al (2020) An organoid biobank of neuroendocrine neoplasms enables genotype-phenotype mapping. Cell 183(5):1420–1435.e21. https://doi.org/10.1016/j.cell.2020.10.023 Nanki K, Toshimitsu K, Takano A et al (2018) Divergent routes toward Wnt and R-spondin niche independency during human gastric carcinogenesis. Cell 174(4):856–869.e17. https://doi.org/10.1016/j.cell.2018.07.027 Pauli C, Hopkins BD, Prandi D et al (2017) Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov 7(5):462–477. https://doi.org/10.1158/2159-8290.CD-16-1154 Wörsdörfer P, I T, Asahina I, et al (2020) Do not keep it simple: recent advances in the generation of complex organoids. J Neural Transm (Vienna) 127(11):1569–1577. https://doi.org/10.1007/s00702-020-02198-8 Ma C, Peng Y, Li H et al (2021) Organ-on-a-chip: a new paradigm for drug development. Trends Pharmacol Sci 42(2):119–133. https://doi.org/10.1016/j.tips.2020.11.009 Trujillo-de Santiago G, Flores-Garza BG, Tavares-Negrete JA et al (2019) The tumor-on-chip: recent advances in the development of microfluidic systems to recapitulate the physiology of solid tumors. Materials (Basel) 12(18):2945. https://doi.org/10.3390/ma12182945 Cherne MD, Sidar B, Sebrell TA et al (2021) A synthetic hydrogel, VitroGel® ORGANOID-3, improves immune cell-epithelial interactions in a tissue chip co-culture model of human gastric organoids and dendritic cells. Front Pharmacol 12:707891. https://doi.org/10.3389/fphar.2021.707891 Lu S, Cuzzucoli F, Jiang J et al (2018) Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing. Lab Chip 18(22):3379–3392. https://doi.org/10.1039/c8lc00852c Chen L, Wei X, Gu D et al (2023) Human liver cancer organoids: biological applications, current challenges, and prospects in hepatoma therapy. Cancer Lett 555:216048. https://doi.org/10.1016/j.canlet.2022.216048 Wang E, Xiang K, Zhang Y et al (2022) Patient-derived organoids (PDOs) and PDO-derived xenografts (PDOXs): new opportunities in establishing faithful pre-clinical cancer models. J Natl Cancer Cent 2(4):263–276. https://doi.org/10.1016/j.jncc.2022.10.001 Gao D, Vela I, Sboner A et al (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell 159(1):176–187. https://doi.org/10.1016/j.cell.2014.08.016 Fujii M, Shimokawa M, Date S et al (2016) A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 18(6):827–838. https://doi.org/10.1016/j.stem.2016.04.003 Lai Y, Wei X, Lin S et al (2017) Current status and perspectives of patient-derived xenograft models in cancer research. J Hematol Oncol 10(1):106. https://doi.org/10.1186/s13045-017-0470-7 Bleijs M, van de Wetering M, Clevers H et al (2019). Xenograft and organoid model systems in cancer research. EMBO J 38(15):e101654. https://doi.org/10.15252/embj.2019101654 Lee SH, Hu W, Matulay JT et al (2018) Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173(2):515–528.e17. https://doi.org/10.1016/j.cell.2018.03.017