{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T21:08:40Z","timestamp":1757624920080,"version":"3.44.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Chulabhorn Foundation"},{"name":"The Royal Golden Jubilee Ph.D. Scholarship Program","award":["PHD\/0060\/2561"],"award-info":[{"award-number":["PHD\/0060\/2561"]}]},{"name":"Chalermphrakiat Grant"},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"crossref","award":["N41A640162"],"award-info":[{"award-number":["N41A640162"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The R.E.D program"},{"name":"The Foundation for Cancer Care Siriraj Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-16144-9","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T10:57:34Z","timestamp":1756205854000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-content confocal analysis of tumorigenesis, cancer stem cells, and drug response in 3D cholangiocarcinoma cultures"],"prefix":"10.1038","volume":"15","author":[{"given":"Krittiyabhorn","family":"Kongtanawanich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supawan","family":"Jamnongsong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Hokland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Methichit","family":"Wattanapanitch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siwanon","family":"Jirawatnotai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"16144_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3389\/fmolb.2020.00033","volume":"7","author":"C Jensen","year":"2020","unstructured":"Jensen, C. & Teng, Y. Is it time to start transitioning from 2D to 3D cell culture?. Front. Mol. Biosci. 7, 33. https:\/\/doi.org\/10.3389\/fmolb.2020.00033 (2020).","journal-title":"Front. Mol. Biosci."},{"key":"16144_CR2","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41392-023-01419-2","volume":"8","author":"Y Liu","year":"2023","unstructured":"Liu, Y. et al. Patient-derived xenograft models in cancer therapy: Technologies and applications. Signal Transduct. Target. Ther. 8, 160. https:\/\/doi.org\/10.1038\/s41392-023-01419-2 (2023).","journal-title":"Signal Transduct. Target. Ther."},{"key":"16144_CR3","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.tips.2022.08.009","volume":"43","author":"A Flobak","year":"2022","unstructured":"Flobak, A., Skanland, S. S., Hovig, E., Tasken, K. & Russnes, H. G. Functional precision cancer medicine: Drug sensitivity screening enabled by cell culture models. Trends Pharmacol. Sci. 43, 973\u2013985. https:\/\/doi.org\/10.1016\/j.tips.2022.08.009 (2022).","journal-title":"Trends Pharmacol. Sci."},{"key":"16144_CR4","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.stem.2024.04.004","volume":"31","author":"JJ Loh","year":"2024","unstructured":"Loh, J. J. & Ma, S. Hallmarks of cancer stemness. Cell Stem Cell 31, 617\u2013639. https:\/\/doi.org\/10.1016\/j.stem.2024.04.004 (2024).","journal-title":"Cell Stem Cell"},{"key":"16144_CR5","doi-asserted-by":"publisher","first-page":"6949","DOI":"10.3390\/ijms24086949","volume":"24","author":"AG Mitrakas","year":"2023","unstructured":"Mitrakas, A. G. et al. Applications and advances of multicellular tumor spheroids: Challenges in their development and analysis. Int. J. Mol. Sci. 24, 6949. https:\/\/doi.org\/10.3390\/ijms24086949 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"16144_CR6","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3389\/fphar.2018.00006","volume":"9","author":"SA Langhans","year":"2018","unstructured":"Langhans, S. A. Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front. Pharmacol. 9, 6. https:\/\/doi.org\/10.3389\/fphar.2018.00006 (2018).","journal-title":"Front. Pharmacol."},{"key":"16144_CR7","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12935-021-01853-8","volume":"21","author":"SJ Han","year":"2021","unstructured":"Han, S. J., Kwon, S. & Kim, K. S. Challenges of applying multicellular tumor spheroids in preclinical phase. Cancer Cell Int. 21, 152. https:\/\/doi.org\/10.1186\/s12935-021-01853-8 (2021).","journal-title":"Cancer Cell Int."},{"key":"16144_CR8","doi-asserted-by":"publisher","DOI":"10.3791\/52671","author":"Y Lombardo","year":"2015","unstructured":"Lombardo, Y., de Giorgio, A., Coombes, C. R., Stebbing, J. & Castellano, L. Mammosphere formation assay from human breast cancer tissues and cell lines. J. Vis. Exp. https:\/\/doi.org\/10.3791\/52671 (2015).","journal-title":"J. Vis. Exp."},{"key":"16144_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064388","volume":"8","author":"CE Smart","year":"2013","unstructured":"Smart, C. E. et al. In vitro analysis of breast cancer cell line tumourspheres and primary human breast epithelia mammospheres demonstrates inter- and intrasphere heterogeneity. PLoS ONE 8, e64388. https:\/\/doi.org\/10.1371\/journal.pone.0064388 (2013).","journal-title":"PLoS ONE"},{"key":"16144_CR10","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3389\/fonc.2017.00293","volume":"7","author":"F Mittler","year":"2017","unstructured":"Mittler, F. et al. High-content monitoring of drug effects in a 3D spheroid model. Front. Oncol. 7, 293. https:\/\/doi.org\/10.3389\/fonc.2017.00293 (2017).","journal-title":"Front. Oncol."},{"key":"16144_CR11","doi-asserted-by":"publisher","first-page":"19103","DOI":"10.1038\/srep19103","volume":"6","author":"M Zanoni","year":"2016","unstructured":"Zanoni, M. et al. 3D tumor spheroid models for in vitro therapeutic screening: A systematic approach to enhance the biological relevance of data obtained. Sci. Rep. 6, 19103. https:\/\/doi.org\/10.1038\/srep19103 (2016).","journal-title":"Sci. Rep."},{"key":"16144_CR12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13045-022-01278-4","volume":"15","author":"H Xu","year":"2022","unstructured":"Xu, H., Jiao, D., Liu, A. & Wu, K. Tumor organoids: Applications in cancer modeling and potentials in precision medicine. J. Hematol. Oncol. 15, 58. https:\/\/doi.org\/10.1186\/s13045-022-01278-4 (2022).","journal-title":"J. Hematol. Oncol."},{"key":"16144_CR13","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s44164-023-00059-8","volume":"2","author":"A Senrung","year":"2023","unstructured":"Senrung, A. et al. 3D tumor spheroids: Morphological alterations a yardstick to anti-cancer drug response. In Vitro Models 2, 219\u2013248. https:\/\/doi.org\/10.1007\/s44164-023-00059-8 (2023).","journal-title":"In Vitro Models"},{"key":"16144_CR14","doi-asserted-by":"publisher","DOI":"10.21769\/bioprotoc.325","volume":"3","author":"S Johnson","year":"2013","unstructured":"Johnson, S., Chen, H. & Lo, P. K. In vitro tumorsphere formation assays. Bio Protocol 3, e325. https:\/\/doi.org\/10.21769\/bioprotoc.325 (2013).","journal-title":"Bio Protocol"},{"key":"16144_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112324","volume":"42","author":"S Mertens","year":"2023","unstructured":"Mertens, S. et al. Drug-repurposing screen on patient-derived organoids identifies therapy-induced vulnerability in KRAS-mutant colon cancer. Cell Rep. 42, 112324. https:\/\/doi.org\/10.1016\/j.celrep.2023.112324 (2023).","journal-title":"Cell Rep."},{"key":"16144_CR16","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.3892\/ijo.2012.1592","volume":"41","author":"X Hong","year":"2012","unstructured":"Hong, X., Chedid, K. & Kalkanis, S. N. Glioblastoma cell line-derived spheres in serum-containing medium versus serum-free medium: A comparison of cancer stem cell properties. Int. J. Oncol. 41, 1693\u20131700. https:\/\/doi.org\/10.3892\/ijo.2012.1592 (2012).","journal-title":"Int. J. Oncol."},{"key":"16144_CR17","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.18632\/oncotarget.6261","volume":"7","author":"CH Lee","year":"2016","unstructured":"Lee, C. H., Yu, C. C., Wang, B. Y. & Chang, W. W. Tumorsphere as an effective in vitro platform for screening anti-cancer stem cell drugs. Oncotarget 7, 1215\u20131226. https:\/\/doi.org\/10.18632\/oncotarget.6261 (2016).","journal-title":"Oncotarget"},{"key":"16144_CR18","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1002\/hep.25745","volume":"56","author":"J Shan","year":"2012","unstructured":"Shan, J. et al. Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology 56, 1004\u20131014. https:\/\/doi.org\/10.1002\/hep.25745 (2012).","journal-title":"Hepatology"},{"key":"16144_CR19","doi-asserted-by":"publisher","first-page":"3214","DOI":"10.1038\/s41598-021-81919-9","volume":"11","author":"L Bhandary","year":"2021","unstructured":"Bhandary, L. et al. Lipid tethering of breast tumor cells reduces cell aggregation during mammosphere formation. Sci. Rep. 11, 3214. https:\/\/doi.org\/10.1038\/s41598-021-81919-9 (2021).","journal-title":"Sci. Rep."},{"key":"16144_CR20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.isci.2018.08.015","volume":"8","author":"PC Bailey","year":"2018","unstructured":"Bailey, P. C. et al. Single-cell tracking of breast cancer cells enables prediction of sphere formation from early cell divisions. iScience 8, 29\u201339. https:\/\/doi.org\/10.1016\/j.isci.2018.08.015 (2018).","journal-title":"iScience"},{"key":"16144_CR21","doi-asserted-by":"publisher","DOI":"10.3791\/55544","author":"SM Maritan","year":"2017","unstructured":"Maritan, S. M., Lian, E. Y. & Mulligan, L. M. An efficient and flexible cell aggregation method for 3D spheroid production. J. Vis. Exp. https:\/\/doi.org\/10.3791\/55544 (2017).","journal-title":"J. Vis. Exp."},{"key":"16144_CR22","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3892\/etm.2017.5419","volume":"15","author":"ZW Zhu","year":"2018","unstructured":"Zhu, Z. W. et al. A novel three-dimensional tumorsphere culture system for the efficient and low-cost enrichment of cancer stem cells with natural polymers. Exp. Ther. Med. 15, 85\u201392. https:\/\/doi.org\/10.3892\/etm.2017.5419 (2018).","journal-title":"Exp. Ther. Med."},{"key":"16144_CR23","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.stemcr.2014.11.002","volume":"4","author":"B Tang","year":"2015","unstructured":"Tang, B. et al. A flexible reporter system for direct observation and isolation of cancer stem cells. Stem Cell Rep. 4, 155\u2013169. https:\/\/doi.org\/10.1016\/j.stemcr.2014.11.002 (2015).","journal-title":"Stem Cell Rep."},{"key":"16144_CR24","doi-asserted-by":"publisher","first-page":"6011","DOI":"10.1158\/0008-5472.CAN-17-0821","volume":"77","author":"Y Huang","year":"2017","unstructured":"Huang, Y. et al. Optical coherence tomography detects necrotic regions and volumetrically quantifies multicellular tumor spheroids. Cancer Res. 77, 6011\u20136020. https:\/\/doi.org\/10.1158\/0008-5472.CAN-17-0821 (2017).","journal-title":"Cancer Res."},{"key":"16144_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73581-8","volume":"14","author":"K Kongtanawanich","year":"2024","unstructured":"Kongtanawanich, K. et al. A live single-cell reporter system reveals drug-induced plasticity of a cancer stem cell-like population in cholangiocarcinoma. Sci. Rep. 14, 22619. https:\/\/doi.org\/10.1038\/s41598-024-73581-8 (2024).","journal-title":"Sci. Rep."},{"key":"16144_CR26","doi-asserted-by":"publisher","first-page":"3983","DOI":"10.1073\/pnas.0530291100","volume":"100","author":"M Al-Hajj","year":"2003","unstructured":"Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. & Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 100, 3983\u20133988. https:\/\/doi.org\/10.1073\/pnas.0530291100 (2003).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"16144_CR27","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/nature03128","volume":"432","author":"SK Singh","year":"2004","unstructured":"Singh, S. K. et al. Identification of human brain tumour initiating cells. Nature 432, 396\u2013401. https:\/\/doi.org\/10.1038\/nature03128 (2004).","journal-title":"Nature"},{"key":"16144_CR28","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nature05372","volume":"445","author":"CA O'Brien","year":"2007","unstructured":"O\u2019Brien, C. A., Pollett, A., Gallinger, S. & Dick, J. E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106\u2013110. https:\/\/doi.org\/10.1038\/nature05372 (2007).","journal-title":"Nature"},{"key":"16144_CR29","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1038\/s41418-021-00878-w","volume":"29","author":"T Velletri","year":"2022","unstructured":"Velletri, T. et al. Single cell-derived spheroids capture the self-renewing subpopulations of metastatic ovarian cancer. Cell Death Differ. 29, 614\u2013626. https:\/\/doi.org\/10.1038\/s41418-021-00878-w (2022).","journal-title":"Cell Death Differ."},{"key":"16144_CR30","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1111\/cas.14504","volume":"111","author":"Y Arima","year":"2020","unstructured":"Arima, Y., Nobusue, H. & Saya, H. Targeting of cancer stem cells by differentiation therapy. Cancer Sci. 111, 2689\u20132695. https:\/\/doi.org\/10.1111\/cas.14504 (2020).","journal-title":"Cancer Sci."},{"key":"16144_CR31","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/978-1-0716-3730-2_11","volume-title":"Cancer Stem Cells: Methods and Protocols","author":"L De Lara-Pe\u00f1a","year":"2024","unstructured":"De Lara-Pe\u00f1a, L. et al. In Cancer Stem Cells: Methods and Protocols (eds Papaccio, F. & Papaccio, G.) 145\u2013161 (Springer, 2024)."},{"key":"16144_CR32","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1016\/j.ajpath.2015.02.010","volume":"185","author":"V Cardinale","year":"2015","unstructured":"Cardinale, V. et al. Profiles of cancer stem cell subpopulations in cholangiocarcinomas. Am. J. Pathol. 185, 1724\u20131739. https:\/\/doi.org\/10.1016\/j.ajpath.2015.02.010 (2015).","journal-title":"Am. J. Pathol."},{"key":"16144_CR33","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.21873\/anticanres.12516","volume":"38","author":"M Kawamoto","year":"2018","unstructured":"Kawamoto, M. et al. Combined gemcitabine and metronidazole is a promising therapeutic strategy for cancer stem-like cholangiocarcinoma. Anticancer Res. 38, 2739\u20132748. https:\/\/doi.org\/10.21873\/anticanres.12516 (2018).","journal-title":"Anticancer Res."},{"key":"16144_CR34","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1038\/s41467-020-15846-0","volume":"11","author":"W Cao","year":"2020","unstructured":"Cao, W. et al. LGR5 marks targetable tumor-initiating cells in mouse liver cancer. Nat. Commun. 11, 1961. https:\/\/doi.org\/10.1038\/s41467-020-15846-0 (2020).","journal-title":"Nat. Commun."},{"key":"16144_CR35","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.3390\/ijms18122574","volume":"18","author":"M Prieto-Vila","year":"2017","unstructured":"Prieto-Vila, M., Takahashi, R. U., Usuba, W., Kohama, I. & Ochiya, T. Drug resistance driven by cancer stem cells and their niche. Int. J. Mol. Sci. 18, 2574. https:\/\/doi.org\/10.3390\/ijms18122574 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"16144_CR36","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.stem.2018.11.011","volume":"24","author":"PB Gupta","year":"2019","unstructured":"Gupta, P. B., Pastushenko, I., Skibinski, A., Blanpain, C. & Kuperwasser, C. Phenotypic plasticity: Driver of cancer initiation, progression, and therapy resistance. Cell Stem Cell 24, 65\u201378. https:\/\/doi.org\/10.1016\/j.stem.2018.11.011 (2019).","journal-title":"Cell Stem Cell"},{"key":"16144_CR37","doi-asserted-by":"publisher","DOI":"10.1002\/anbr.202100017","volume":"1","author":"E Dogan","year":"2021","unstructured":"Dogan, E. et al. Cancer stem cells in tumor modeling: Challenges and future directions. Adv. Nanobiomed. Res. 1, 2100017. https:\/\/doi.org\/10.1002\/anbr.202100017 (2021).","journal-title":"Adv. Nanobiomed. Res."},{"key":"16144_CR38","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s13577-021-00642-9","volume":"35","author":"OE Atat","year":"2022","unstructured":"Atat, O. E. et al. 3D modeling in cancer studies. Hum. Cell 35, 23\u201336. https:\/\/doi.org\/10.1007\/s13577-021-00642-9 (2022).","journal-title":"Hum. Cell"},{"key":"16144_CR39","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.3390\/cells8121620","volume":"8","author":"NE Ryu","year":"2019","unstructured":"Ryu, N. E., Lee, S. H. & Park, H. Spheroid culture system methods and applications for mesenchymal stem cells. Cells 8, 1620. https:\/\/doi.org\/10.3390\/cells8121620 (2019).","journal-title":"Cells"},{"key":"16144_CR40","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1111\/cas.13155","volume":"108","author":"T Ishiguro","year":"2017","unstructured":"Ishiguro, T. et al. Tumor-derived spheroids: Relevance to cancer stem cells and clinical applications. Cancer Sci. 108, 283\u2013289. https:\/\/doi.org\/10.1111\/cas.13155 (2017).","journal-title":"Cancer Sci."},{"key":"16144_CR41","doi-asserted-by":"publisher","first-page":"926","DOI":"10.3390\/ph15080926","volume":"15","author":"SM Badr-Eldin","year":"2022","unstructured":"Badr-Eldin, S. M., Aldawsari, H. M., Kotta, S., Deb, P. K. & Venugopala, K. N. Three-dimensional in vitro cell culture models for efficient drug discovery: Progress so far and future prospects. Pharmaceuticals (Basel) 15, 926. https:\/\/doi.org\/10.3390\/ph15080926 (2022).","journal-title":"Pharmaceuticals (Basel)"},{"key":"16144_CR42","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.3390\/cancers14041023","volume":"14","author":"H Ozkan","year":"2022","unstructured":"Ozkan, H., Ozturk, D. G. & Korkmaz, G. Transcriptional factor repertoire of breast cancer in 3D cell culture models. Cancers (Basel) 14, 1023. https:\/\/doi.org\/10.3390\/cancers14041023 (2022).","journal-title":"Cancers (Basel)"},{"key":"16144_CR43","doi-asserted-by":"publisher","first-page":"3245","DOI":"10.1021\/acs.analchem.1c04959","volume":"94","author":"P Li","year":"2022","unstructured":"Li, P. et al. Selective single-cell expansion on a microfluidic chip for studying heterogeneity of glioma stem cells. Anal. Chem. 94, 3245\u20133253. https:\/\/doi.org\/10.1021\/acs.analchem.1c04959 (2022).","journal-title":"Anal. Chem."},{"key":"16144_CR44","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1477-5956-12-39","volume":"12","author":"U Rajcevic","year":"2014","unstructured":"Rajcevic, U. et al. Colorectal cancer derived organotypic spheroids maintain essential tissue characteristics but adapt their metabolism in culture. Proteome Sci. 12, 39. https:\/\/doi.org\/10.1186\/1477-5956-12-39 (2014).","journal-title":"Proteome Sci."},{"key":"16144_CR45","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.818437","volume":"12","author":"ML Lotsberg","year":"2022","unstructured":"Lotsberg, M. L. et al. Intrinsic differences in spatiotemporal organization and stromal cell interactions between isogenic lung cancer cells of epithelial and mesenchymal phenotypes revealed by high-dimensional single-cell analysis of heterotypic 3D spheroid models. Front. Oncol. 12, 818437. https:\/\/doi.org\/10.3389\/fonc.2022.818437 (2022).","journal-title":"Front. Oncol."},{"key":"16144_CR46","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1386097","volume":"14","author":"BS Nielsen","year":"2024","unstructured":"Nielsen, B. S. et al. Architectural organization and molecular profiling of 3D cancer heterospheroids and their application in drug testing. Front. Oncol. 14, 1386097. https:\/\/doi.org\/10.3389\/fonc.2024.1386097 (2024).","journal-title":"Front. Oncol."},{"key":"16144_CR47","doi-asserted-by":"publisher","first-page":"5319","DOI":"10.1038\/s41598-017-18815-8","volume":"8","author":"MA Borten","year":"2018","unstructured":"Borten, M. A., Bajikar, S. S., Sasaki, N., Clevers, H. & Janes, K. A. Automated brightfield morphometry of 3D organoid populations by OrganoSeg. Sci. Rep. 8, 5319. https:\/\/doi.org\/10.1038\/s41598-017-18815-8 (2018).","journal-title":"Sci. Rep."},{"key":"16144_CR48","doi-asserted-by":"publisher","first-page":"E2490","DOI":"10.1073\/pnas.1220353110","volume":"110","author":"A Humphries","year":"2013","unstructured":"Humphries, A. et al. Lineage tracing reveals multipotent stem cells maintain human adenomas and the pattern of clonal expansion in tumor evolution. Proc. Natl. Acad. Sci. U.S.A. 110, E2490-2499. https:\/\/doi.org\/10.1073\/pnas.1220353110 (2013).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"16144_CR49","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/nature10762","volume":"481","author":"M Greaves","year":"2012","unstructured":"Greaves, M. & Maley, C. C. Clonal evolution in cancer. Nature 481, 306\u2013313. https:\/\/doi.org\/10.1038\/nature10762 (2012).","journal-title":"Nature"},{"key":"16144_CR50","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-024-00960-8","author":"J Kalla","year":"2024","unstructured":"Kalla, J., Pfneissl, J., Mair, T., Tran, L. & Egger, G. A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine. Cell Oncol. (Dordr.) https:\/\/doi.org\/10.1007\/s13402-024-00960-8 (2024).","journal-title":"Cell Oncol. (Dordr.)"},{"key":"16144_CR51","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105182","volume":"25","author":"S Jamnongsong","year":"2022","unstructured":"Jamnongsong, S. et al. Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma. iScience 25, 105182. https:\/\/doi.org\/10.1016\/j.isci.2022.105182 (2022).","journal-title":"iScience"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-16144-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-16144-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-16144-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T16:25:03Z","timestamp":1757435103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-16144-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["16144"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-16144-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"assertion":[{"value":"28 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"31387"}}