[ 1 ] Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136(5):E359–86. 链接1

[ 2 ] Onyoh EF, Hsu WF, Chang LC, Lee YC, Wu MS, Chiu HM. The rise of colorectal cancer in Asia: epidemiology, screening, and management. Curr Gastroenterol Rep 2019;21(8):36. 链接1

[ 3 ] Kanji ZS, Gallinger S. Diagnosis and management of pancreatic cancer. CMAJ 2013;185(14):1219–26. 链接1

[ 4 ] Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2016;2(1):16018. 链接1

[ 5 ] Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009;459(7244):262–5. 链接1

[ 6 ] Sato T, Stange DE, Ferrante M, Vries RGJ, van Es JH, van den Brink S, et al. Longterm expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 2011;141 (5):1762–72. 链接1

[ 7 ] Jung P, Sato T, Merlos-Suárez A, Barriga FM, Iglesias M, Rossell D, et al. Isolation and in vitro expansion of human colonic stem cells. Nat Med 2011;17 (10):1225–7. 链接1

[ 8 ] Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen MA, et al. Longterm culture of genome-stable bipotent stem cells from adult human liver. Cell 2015;160(1–2):299–312. 链接1

[ 9 ] Boj SF, Hwang CI, Baker LA, Chio II, Engle DD, Corbo V, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 2015;160(1–2):324–38. 链接1

[10] Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 2015;148(1):126–36.e6.

[11] Maimets M, Rocchi C, Bron R, Pringle S, Kuipers J, Giepmans BG, et al. Longterm in vitro expansion of salivary gland stem cells driven by Wnt signals. Stem Cell Rep 2016;6(1):150–62. 链接1

[12] DeWard A, Cramer J, Lagasse E. Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep 2014;9(2):701–11. 链接1

[13] Schwank G, Koo BK, Sasselli V, Dekkers J, Heo I, Demircan T, et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 2013;13(6):653–8. 链接1

[14] Turner DA, Girgin M, Alonso-Crisostomo L, Trivedi V, Baillie-Johnson P, Glodowski CR, et al. Anteroposterior polarity and elongation in the absence of extra-embryonic tissues and of spatially localised signalling in gastruloids: mammalian embryonic organoids. Development 2017;144(21):3894–906. 链接1

[15] Bershteyn M, Nowakowski TJ, Pollen AA, Di Lullo E, Nene A, Wynshaw-Boris A, et al. Human iPSC-derived cerebral organoids model cellular features of lissencephaly and reveal prolonged mitosis of outer radial glia. Cell Stem Cell 2017;20(4):435–49.e4.

[16] Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, et al. Lgr5+ve stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 2010;6(1):25–36. 链接1

[17] Huch M, Dorrell C, Boj SF, van Es JH, Li VSW, van de Wetering M, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 2013;494(7436):247–50. 链接1

[18] Huch M, Bonfanti P, Boj SF, Sato T, Loomans CJM, van de Wetering M, et al. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J 2013;32(20):2708–21. 链接1

[19] Papapetrou EP. Patient-derived induced pluripotent stem cells in cancer research and precision oncology. Nat Med 2016;22(12):1392–401. 链接1

[20] Fujii M, Matano M, Nanki K, Sato T. Efficient genetic engineering of human intestinal organoids using electroporation. Nat Protoc 2015;10(10):1474–85. 链接1

[21] Bertaux-Skeirik N, Centeno J, Gao J, Gabre J, Zavros Y. Oncogenic transformation of human-derived gastric organoids. Methods Mol Biol 2019;1576:205–13. 链接1

[22] Hahn S, Yoo J. Gastrointestinal epithelial organoid cultures from postsurgical tissues. Methods Mol Biol 2019;1576:327–37. 链接1

[23] Yin X, Mead B, Safaee H, Langer R, Karp J, Levy O. Engineering stem cell organoids. Cell Stem Cell 2016;18(1):25–38. 链接1

[24] Broda TR, McCracken KW, Wells JM. Generation of human antral and fundic gastric organoids from pluripotent stem cells. Nat Protoc 2019;14 (1):28–50. 链接1

[25] Hannan NF, Fordham R, Syed Y, Moignard V, Berry A, Bautista R, et al. Generation of multipotent foregut stem cells from human pluripotent stem cells. Stem Cell Rep 2013;1(4):293–306. 链接1

[26] McCracken KW, Catá EM, Crawford CM, Sinagoga KL, Schumacher M, Rockich BE, et al. Modelling human development and disease in pluripotent stem-cellderived gastric organoids. Nature 2014;516(7531):400–4. 链接1

[27] Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 2011;470(7332):105–9. 链接1

[28] Uchida H, Machida M, Miura T, Kawasaki T, Okazaki T, Sasaki K, et al. A xenogeneic-free system generating functional human gut organoids from pluripotent stem cells. JCI Insight 2017;2(1):e86492. 链接1

[29] D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 2005;23(12):1534–41. 链接1

[30] Clevers H, Loh KM, Nusse R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 2014;346(6205):1248012. 链接1

[31] Van Camp JK, Beckers S, Zegers D, Van Hul W. Wnt signaling and the control of human stem cell fate. Stem Cell Rev Rep 2014;10(2):207–29. 链接1

[32] Qi Z, Li Y, Zhao B, Xu C, Liu Y, Li H, et al. BMP restricts stemness of intestinal Lgr5+ stem cells by directly suppressing their signature genes. Nat Commun 2017;8(1):13824. 链接1

[33] He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, et al. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-bcatenin signaling. Nat Genet 2004;36(10):1117–21. 链接1

[34] Lv YQ, Wu J, Li XK, Zhang JS, Bellusci S. Role of FGF10/FGFR2b signaling in mouse digestive tract development, repair and regeneration following injury. Front Cell Dev Biol 2019;7:326. 链接1

[35] Todisco A, Mao M, Keeley TM, Ye W, Samuelson LC, Eaton KA. Regulation of gastric epithelial cell homeostasis by gastrin and bone morphogenetic protein signaling. Physiol Rep 2015;3(8):3. 链接1

[36] Watanabe K, Ueno M, Kamiya D, Nishiyama A, Matsumura M, Wataya T, et al. A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol 2007;25(6):681–6. 链接1

[37] Massagué J, Seoane J, Wotton D. Smad transcription factors. Genes Dev 2005;19(23):2783–810. 链接1

[38] Shi Y, Massagué J. Mechanisms of TGF-b signaling from cell membrane to the nucleus. Cell 2003;113(6):685–700. 链接1

[39] Jung B, Staudacher JJ, Beauchamp D. Transforming growth factor b superfamily signaling in development of colorectal cancer. Gastroenterology 2017;152 (1):36–52. 链接1

[40] Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, et al. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 2009;136(6): 1136–47. 链接1

[41] Hynes RO. The extracellular matrix: not just pretty fibrils. Science 2009;326 (5957):1216–9. 链接1

[42] Yang L, Yang S, Li X, Li B, Li Y, Zhang X, et al. Tumor organoids: from inception to future in cancer research. Cancer Lett 2019;454:120–33. 链接1

[43] Hughes CS, Postovit LM, Lajoie GA. Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 2010;10 (9):1886–90. 链接1

[44] Sampaziotis F, Muraro D, Tysoe OC, Sawiak S, Beach TE, Godfrey EM, et al. Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science 2021;371(6531):839–46. 链接1

[45] Li X, Francies HE, Secrier M, Perner J, Miremadi A, Galeano-Dalmau N, et al. Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nat Commun 2018;9(1):2983. 链接1

[46] Kijima T, Nakagawa H, Shimonosono M, Chandramouleeswaran PM, Hara T, Sahu V, et al. Three-dimensional organoids reveal therapy resistance of esophageal and oropharyngeal squamous cell carcinoma cells. Cell Mol Gastroenterol Hepatol 2019;7(1):73–91. 链接1

[47] Pauli C, Hopkins BD, Prandi D, Shaw R, Fedrizzi T, Sboner A, et al. Personalized in vitro and in vivo cancer nodels to guide precision medicine. Cancer Discov 2017;7(5):462–77. 链接1

[48] Van de Wetering M, Francies H, Francis J, Bounova G, Iorio F, Pronk A, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 2015;161(4):933–45. 链接1

[49] Fujii M, Shimokawa M, Date S, Takano A, Matano M, Nanki K, et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 2016;18(6):827–38. 链接1

[50] Broutier L, Mastrogiovanni G, Verstegen MMA, Francies HE, Gavarró LM, Bradshaw CR, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med 2017;23(12):1424–35. 链接1

[51] Huang L, Holtzinger A, Jagan I, BeGora M, Lohse I, Ngai N, 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. 链接1

[52] Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487(7407):330–7. 链接1

[53] Sun L, Wang Y, Cen J, Ma X, Cui L, Qiu Z, et al. Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes. Nat Cell Biol 2019;21(8):1015–26. 链接1

[54] Seino T, Kawasaki S, Shimokawa M, Tamagawa H, Toshimitsu K, Fujii M, et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell 2018;22(3):454–67.e6.

[55] Zhang HC, Kuo CJ. Personalizing pancreatic cancer organoids with hPSCs. Nat Med 2015;21(11):1249–51. 链接1

[56] De Flora S, Bonanni P. The prevention of infection-associated cancers. Carcinogenesis 2011;32(6):787–95. 链接1

[57] Drost J, Clevers H. Translational applications of adult stem cell-derived organoids. Development 2017;144(6):968–75. 链接1

[58] Scanu T, Spaapen R, Bakker J, Pratap C, Wu LE, Hofland I, et al. Salmonella manipulation of host signaling pathways provokes cellular transformation associated with gallbladder carcinoma. Cell Host Microbe 2015;17(6):763–74. 链接1

[59] Yin Y, Bijvelds M, Dang W, Xu L, van der Eijk AA, Knipping K, et al. Modeling rotavirus infection and antiviral therapy using primary intestinal organoids. Antiviral Res 2015;123:120–31. 链接1

[60] Behjati S, Huch M, van Boxtel R, Karthaus W, Wedge DC, Tamuri AU, et al. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 2014;513(7518):422–5. 链接1

[61] Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature 2009;458 (7239):719–24. 链接1

[62] Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012;483(7391):603–7. 链接1

[63] Masters JRW. Human cancer cell lines: fact and fantasy. Nat Rev Mol Cell Biol 2000;1(3):233–6. 链接1

[64] Komor AC, Badran AH, Liu DR. CRISPR-based technologies for the manipulation of eukaryotic genomes. Cell 2017;169(3):559. 链接1

[65] Drost J, van Jaarsveld RH, Ponsioen B, Zimberlin C, van Boxtel R, Buijs A, et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature 2015;521(7550):43–7. 链接1

[66] Matano M, Date S, Shimokawa M, Takano A, Fujii M, Ohta Y, et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med 2015;21(3):256–62. 链接1

[67] Lee J, Snyder ER, Liu Y, Gu X, Wang J, Flowers BM, et al. Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells. Nat Commun 2017;8(1):14686. 链接1

[68] Li L, Knutsdottir H, Hui K, Weiss MJ, He J, Philosophe B, et al. Human primary liver cancer organoids reveal intratumor and interpatient drug response heterogeneity. JCI Insight 2019;4(2):4. 链接1

[69] Kamb A. What’s wrong with our cancer models? Nat Rev Drug Discov 2005;4(2):161–5. 链接1

[70] Caponigro G, Sellers WR. Advances in the preclinical testing of cancer therapeutic hypotheses. Nat Rev Drug Discov 2011;10(3):179–87. 链接1

[71] Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernández-Mateos J, Khan K, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 2018;359(6378):920–6. 链接1

[72] Yao Y, Xu X, Yang L, Zhu J, Wan J, Shen L, et al. Patient-derived organoids predict chemoradiation responses of locally advanced rectal cancer. Cell Stem Cell 2020;26(1):17–26.e6. 链接1

[73] Ganesh K, Wu C, O’Rourke KP, Szeglin BC, Zheng Y, Sauvé CE, et al. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat Med 2019;25(10):1607–14. 链接1

[74] Weeber F, Ooft SN, Dijkstra KK, Voest EE. Tumor organoids as a pre-clinical cancer model for drug discovery. Cell Chem Biol 2017;24(9):1092–100. 链接1

[75] Saito Y. Establishment of an organoid bank of biliary tract and pancreatic cancers and its application for personalized therapy and future treatment. J Gastroenterol Hepatol 2019;34(11):1906–10. 链接1

[76] Yan HHN, Siu HC, Law S, Ho SL, Yue SSK, Tsui WY, et al. A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening. Cell Stem Cell 2018;23(6):882–97.e11.

[77] Saito Y, Muramatsu T, Kanai Y, Ojima H, Sukeda A, Hiraoka N, et al. Establishment of patient-derived organoids and drug screening for biliary tract carcinoma. Cell Rep 2019;27(4):1265–76.e4.

[78] Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer 2018;18 (7):407–18. 链接1

[79] Finnberg NK, Gokare P, Lev A, Grivennikov SI, MacFarlane AW, Campbell KS, et al. Application of 3D tumoroid systems to define immune and cytotoxic therapeutic responses based on tumoroid and tissue slice culture molecular signatures. Oncotarget 2017;8(40):66747–57. 链接1

[80] Neal JT, Li X, Zhu J, Giangarra V, Grzeskowiak CL, Ju J, et al. Organoid modeling of the tumor immune microenvironment. Cell 2018;175(7):1972– 88.e16.

[81] Dijkstra KK, Cattaneo CM, Weeber F, Chalabi M, van de Haar J, Fanchi LF, et al. Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids. Cell 2018;174(6):1586–98.e12.

[82] Chakrabarti J, Holokai L, Syu L, Steele N, Chang J, Dlugosz A, et al. Mousederived gastric organoid and immune cell co-culture for the study of the tumor microenvironment. Methods Mol Biol 2018;1817:157–68. 链接1

[83] Schnalzger TE, de Groot MH, Zhang C, Mosa MH, Michels BE, Röder J, et al. 3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids. EMBO J 2019;38(12):38. 链接1

[84] Workman MJ, Mahe MM, Trisno S, Poling HM, Watson CL, Sundaram N, et al. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med 2017;23(1):49–59. 链接1

[85] Öhlund D, Handly-Santana A, Biffi G, Elyada E, Almeida AS, Ponz-Sarvise M, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med 2017;214(3):579–96. 链接1

[86] Kim E, Choi S, Kang B, Kong J, Kim Y, Yoon WH, et al. Creation of bladder assembloids mimicking tissue regeneration and cancer. Nature 2020;588 (7839):664–9. 链接1