{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:22:44Z","timestamp":1762424564307,"version":"build-2065373602"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"The Thailand Science Research and Innovation Fund, and the University of Phayao","award":["5129\/2567"],"award-info":[{"award-number":["5129\/2567"]}]},{"name":"The University of Phayao, School of Medicine","award":["MD66-03"],"award-info":[{"award-number":["MD66-03"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Oncol"],"DOI":"10.1007\/s12032-025-03078-5","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:20Z","timestamp":1760122760000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and transcriptomic alterations underlying aggressiveness in 5-fluorouracil-resistant HCT116 cells"],"prefix":"10.1007","volume":"42","author":[{"given":"Pornchai","family":"Sooksaen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthid","family":"Thim-uam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratsada","family":"Praphasawat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chutamas","family":"Thepmalee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanokkarn","family":"Phromnoi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damratsamon","family":"Surangkul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surisak","family":"Prasarnpun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chakkraphong","family":"Khonthun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"3078_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17\u201348. https:\/\/doi.org\/10.3322\/caac.21763.","journal-title":"CA Cancer J Clin"},{"key":"3078_CR2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229\u201363. https:\/\/doi.org\/10.3322\/caac.21834.","journal-title":"CA Cancer J Clin"},{"key":"3078_CR3","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1136\/gutjnl-2022-327736","volume":"72","author":"E Morgan","year":"2023","unstructured":"Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag C, Laversanne M, et al. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023;72:338\u201344.","journal-title":"Gut"},{"key":"3078_CR4","doi-asserted-by":"publisher","first-page":"2200028","DOI":"10.1002\/mnfr.202200028","volume":"66","author":"L Wang","year":"2022","unstructured":"Wang L, Shannar AAF, Wu R, Chou P, Sarwar MS, Kuo H-C, et al. Butyrate drives metabolic rewiring and epigenetic reprogramming in human colon cancer cells. Mol Nutr Food Res. 2022;66:2200028. https:\/\/doi.org\/10.1002\/mnfr.202200028.","journal-title":"Mol Nutr Food Res"},{"key":"3078_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.adcanc.2024.100114","volume":"10","author":"S Ashique","year":"2024","unstructured":"Ashique S, Bhowmick M, Pal R, Khatoon H, Kumar P, Sharma H, et al. Multi drug resistance in colorectal cancer- approaches to overcome, advancements and future success. Adv Cancer Biol-Metastasis. 2024;10:100114. https:\/\/doi.org\/10.1016\/j.adcanc.2024.100114.","journal-title":"Adv Cancer Biol-Metastasis"},{"key":"3078_CR6","doi-asserted-by":"publisher","first-page":"854","DOI":"10.3390\/biology10090854","volume":"10","author":"S Azwar","year":"2021","unstructured":"Azwar S, Seow HF, Abdullah M, Faisal Jabar M, Mohtarrudin N. Recent updates on mechanisms of resistance to 5-fluorouracil and reversal strategies in colon cancer treatment. Biology. 2021;10:854.","journal-title":"Biology"},{"key":"3078_CR7","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.7150\/jca.19079","volume":"8","author":"Z-S Jiang","year":"2017","unstructured":"Jiang Z-S, Sun Y-Z, Wang S-M, Ruan J-S. Epithelial-mesenchymal transition: potential regulator of ABC transporters in tumor progression. J Cancer. 2017;8:2319.","journal-title":"J Cancer"},{"key":"3078_CR8","doi-asserted-by":"publisher","first-page":"5831","DOI":"10.1007\/s11033-019-05017-w","volume":"46","author":"A D\u0142ugosz-Pokorska","year":"2019","unstructured":"D\u0142ugosz-Pokorska A, Pi\u0119ta M, Janecki T, Janecka A. New uracil analogs as downregulators of ABC transporters in 5-fluorouracil-resistant human leukemia HL-60 cell line. Mol Biol Rep. 2019;46:5831\u20139. https:\/\/doi.org\/10.1007\/s11033-019-05017-w.","journal-title":"Mol Biol Rep"},{"key":"3078_CR9","doi-asserted-by":"publisher","DOI":"10.1177\/15330338221081219","volume":"21","author":"Q Ni","year":"2022","unstructured":"Ni Q, Li M, Yu S. Research progress of epithelial-mesenchymal transition treatment and drug resistance in colorectal cancer. Technol Cancer Res Treat. 2022;21:15330338221081219. https:\/\/doi.org\/10.1177\/15330338221081219.","journal-title":"Technol Cancer Res Treat"},{"key":"3078_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13163949","author":"F Rascio","year":"2021","unstructured":"Rascio F, Spadaccino F, Rocchetti MT, Castellano G, Stallone G, Netti GS, et al. The pathogenic role of PI3K\/AKT pathway in cancer onset and drug resistance: an updated review. Cancers. 2021. https:\/\/doi.org\/10.3390\/cancers13163949.","journal-title":"Cancers"},{"key":"3078_CR11","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S265531","author":"Y Kan","year":"2020","unstructured":"Kan Y, Liu J, Li F. High expression of nuclear transcription factor-\u03baB is associated with cisplatin resistance and prognosis for ovarian cancer. Cancer Manag Res. 2020. https:\/\/doi.org\/10.2147\/CMAR.S265531.","journal-title":"Cancer Manag Res"},{"key":"3078_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26031168","volume":"26","author":"G Valenzuela","year":"2025","unstructured":"Valenzuela G, Contreras HR, Marcelain K, Burotto M, Gonz\u00e1lez-Montero J. Understanding microrna-mediated chemoresistance in colorectal cancer treatment. Int J Mol Sci. 2025;26:1168.","journal-title":"Int J Mol Sci"},{"key":"3078_CR13","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S257700","author":"E Entezar-Almahdi","year":"2020","unstructured":"Entezar-Almahdi E, Mohammadi-Samani S, Tayebi L, Farjadian F. Recent advances in designing 5-fluorouracil delivery systems: a stepping stone in the safe treatment of colorectal cancer. Int J Nanomed. 2020. https:\/\/doi.org\/10.2147\/IJN.S257700.","journal-title":"Int J Nanomed"},{"key":"3078_CR14","doi-asserted-by":"publisher","first-page":"5321","DOI":"10.1038\/s41467-020-19173-2","volume":"11","author":"Y-H Cho","year":"2020","unstructured":"Cho Y-H, Ro EJ, Yoon J-S, Mizutani T, Kang D-W, Park J-C, et al. 5-FU promotes stemness of colorectal cancer via p53-mediated WNT\/\u03b2-catenin pathway activation. Nat Commun. 2020;11:5321. https:\/\/doi.org\/10.1038\/s41467-020-19173-2.","journal-title":"Nat Commun"},{"key":"3078_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115902","volume":"218","author":"J Hu","year":"2023","unstructured":"Hu J, Li A, Guo Y, Ma T, Feng S. The relationship between tumor metabolism and 5-fluorouracil resistance. Biochem Pharmacol. 2023;218:115902. https:\/\/doi.org\/10.1016\/j.bcp.2023.115902.","journal-title":"Biochem Pharmacol"},{"key":"3078_CR16","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13578-017-0145-7","volume":"7","author":"L Zhang","year":"2017","unstructured":"Zhang L, Song R, Gu D, Zhang X, Yu B, Liu B, et al. The role of GLI1 for 5-Fu resistance in colorectal cancer. Cell Biosci. 2017;7:17. https:\/\/doi.org\/10.1186\/s13578-017-0145-7.","journal-title":"Cell Biosci"},{"key":"3078_CR17","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41392-024-01953-7","volume":"9","author":"Q Li","year":"2024","unstructured":"Li Q, Geng S, Luo H, Wang W, Mo Y-Q, Luo Q, et al. Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy. Signal Transduct Target Ther. 2024;9:266. https:\/\/doi.org\/10.1038\/s41392-024-01953-7.","journal-title":"Signal Transduct Target Ther"},{"key":"3078_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0128-8","volume":"50","author":"L He","year":"2018","unstructured":"He L, Zhu H, Zhou S, Wu T, Wu H, Yang H, et al. Wnt pathway is involved in 5-FU drug resistance of colorectal cancer cells. Exp Mol Med. 2018;50:1\u201312. https:\/\/doi.org\/10.1038\/s12276-018-0128-8.","journal-title":"Exp Mol Med"},{"key":"3078_CR19","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11744","volume":"23","author":"G-X Zhu","year":"2021","unstructured":"Zhu G-X, Gao D, Shao Z-Z, Chen L, Ding W-J, Yu Q-F. Wnt\/\u03b2-catenin signaling: causes and treatment targets of drug resistance in colorectal cancer (review). Mol Med Rep. 2021;23:105. https:\/\/doi.org\/10.3892\/mmr.2020.11744.","journal-title":"Mol Med Rep"},{"key":"3078_CR20","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1177\/1758834015614530","volume":"8","author":"WA Hammond","year":"2016","unstructured":"Hammond WA, Swaika A, Mody K. Pharmacologic resistance in colorectal cancer: a review. Therapeutic Adv Med Oncol. 2016;8:57\u201384.","journal-title":"Therapeutic Adv Med Oncol"},{"key":"3078_CR21","doi-asserted-by":"publisher","first-page":"257","DOI":"10.20517\/cdr.2022.136","volume":"6","author":"HG William","year":"2023","unstructured":"William HG, Charles Chidi O. Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects. Cancer Drug Resist. 2023;6:257\u201372. https:\/\/doi.org\/10.20517\/cdr.2022.136.","journal-title":"Cancer Drug Resist"},{"key":"3078_CR22","doi-asserted-by":"publisher","first-page":"175253","DOI":"10.1016\/j.ejphar.2022.175253","volume":"933","author":"ACM Sousa-Squiavinato","year":"2022","unstructured":"Sousa-Squiavinato ACM, Arregui Ramos DA, Wagner MS, Tessmann JW, de Freitas-Junior JCM, Morgado-D\u00edaz JA. Long-term resistance to 5-fluorouracil promotes epithelial\u2013mesenchymal transition, apoptosis evasion, autophagy, and reduced proliferation rate in colon cancer cells. Eur J Pharmacol. 2022;933:175253. https:\/\/doi.org\/10.1016\/j.ejphar.2022.175253.","journal-title":"Eur J Pharmacol"},{"key":"3078_CR23","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13065-024-01173-8","volume":"18","author":"AH Faid","year":"2024","unstructured":"Faid AH, Ramadan MA. Reducing the effective dose of cisplatin using cobalt modified silver nano-hybrid as a carriers on MCF7 and HCT cell models. BMC Chem. 2024;18:69. https:\/\/doi.org\/10.1186\/s13065-024-01173-8.","journal-title":"BMC Chem"},{"key":"3078_CR24","doi-asserted-by":"publisher","first-page":"36855","DOI":"10.1038\/srep36855","volume":"6","author":"SA Khaleel","year":"2016","unstructured":"Khaleel SA, Al-Abd AM, Ali AA, Abdel-Naim AB. Didox and resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity. Sci Rep. 2016;6:36855. https:\/\/doi.org\/10.1038\/srep36855.","journal-title":"Sci Rep"},{"key":"3078_CR25","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.3892\/or.2016.4838","volume":"36","author":"HR Kang","year":"2016","unstructured":"Kang HR, Choi HG, Jeon CK, Lim S-J, Kim SH. Butyrate-mediated acquisition of chemoresistance by human colon cancer cells. Oncol Rep. 2016;36:1119\u201326. https:\/\/doi.org\/10.3892\/or.2016.4838.","journal-title":"Oncol Rep"},{"key":"3078_CR26","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3249766","volume":"2022","author":"BXJ Tune","year":"2022","unstructured":"Tune BXJ, Sim MS, Poh CL, Guad RM, Woon CK, Hazarika I, et al. Matrix metalloproteinases in chemoresistance: regulatory roles, molecular interactions, and potential inhibitors. J Oncol. 2022;2022:3249766. https:\/\/doi.org\/10.1155\/2022\/3249766.","journal-title":"J Oncol"},{"issue":"14","key":"3078_CR27","doi-asserted-by":"publisher","first-page":"4813","DOI":"10.3390\/app10144813","volume":"10","author":"K Komoshvili","year":"2020","unstructured":"Komoshvili K, Israel K, Levitan J, Yahalom A, Barbora A, Liberman-Aronov S. W-band millimeter waves targeted mortality of H1299 human lung cancer cells without affecting non-tumorigenic MCF-10A human epithelial cells in vitro. Appl Sci. 2020;10(14):4813.","journal-title":"Appl Sci"},{"key":"3078_CR28","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.18632\/oncotarget.27974","volume":"12","author":"L Alhalhooly","year":"2021","unstructured":"Alhalhooly L, Mamnoon B, Kim J, Mallik S, Choi Y. Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy. Oncotarget. 2021;12:1165.","journal-title":"Oncotarget"},{"key":"3078_CR29","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.canlet.2015.02.045","volume":"361","author":"H-Z Yang","year":"2015","unstructured":"Yang H-Z, Ma Y, Zhou Y, Xu L-M, Chen X-J, Ding W-B, et al. Autophagy contributes to the enrichment and survival of colorectal cancer stem cells under oxaliplatin treatment. Cancer Lett. 2015;361:128\u201336.","journal-title":"Cancer Lett"},{"key":"3078_CR30","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1186\/s12885-016-2906-9","volume":"16","author":"A Belounis","year":"2016","unstructured":"Belounis A, Nyalendo C, Le Gall R, Imbriglio TV, Mahma M, Teira P, et al. Autophagy is associated with chemoresistance in neuroblastoma. BMC Cancer. 2016;16:891. https:\/\/doi.org\/10.1186\/s12885-016-2906-9.","journal-title":"BMC Cancer"},{"key":"3078_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109415","volume":"119","author":"X Li","year":"2019","unstructured":"Li X, Zhou Y, Li Y, Yang L, Ma Y, Peng X, et al. Autophagy: a novel mechanism of chemoresistance in cancers. Biomed Pharmacother. 2019;119:109415. https:\/\/doi.org\/10.1016\/j.biopha.2019.109415.","journal-title":"Biomed Pharmacother"},{"key":"3078_CR32","doi-asserted-by":"publisher","first-page":"151","DOI":"10.5487\/TR.2015.31.2.151","volume":"31","author":"AY Kim","year":"2015","unstructured":"Kim AY, Kwak J-H, Je NK, Lee Y-h, Jung Y-S. Epithelial-mesenchymal transition is associated with acquired resistance to 5-fluorocuracil in HT-29 colon cancer cells. Toxicol Res. 2015;31:151\u20136. https:\/\/doi.org\/10.5487\/TR.2015.31.2.151.","journal-title":"Toxicol Res"},{"key":"3078_CR33","doi-asserted-by":"publisher","first-page":"16378","DOI":"10.1038\/s41598-019-52816-z","volume":"9","author":"T Ieda","year":"2019","unstructured":"Ieda T, Tazawa H, Okabayashi H, Yano S, Shigeyasu K, Kuroda S, et al. Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment\u2013colorectal cancer network. Sci Rep. 2019;9:16378. https:\/\/doi.org\/10.1038\/s41598-019-52816-z.","journal-title":"Sci Rep"},{"key":"3078_CR34","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1080\/08820139.2019.1595643","volume":"48","author":"NA Kazemi Sefat","year":"2019","unstructured":"Kazemi Sefat NA, Mohammadi MM, Hadjati J, Talebi S, Ajami M, Daneshvar HJIi. Sodium butyrate as a histone deacetylase inhibitor affects toll-like receptor 4 expression in colorectal cancer cell lines. Immunol Invest. 2019;48:759\u201369.","journal-title":"Immunol Invest"},{"key":"3078_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/biom12121786","volume":"12","author":"M Franchi","year":"2022","unstructured":"Franchi M, Karamanos K-A, Cappadone C, Calonghi N, Greco N, Franchi L, et al. Substrate type and concentration differently affect colon cancer cells ultrastructural morphology, EMT markers, and matrix degrading enzymes. Biomolecules. 2022;12:1786.","journal-title":"Biomolecules"},{"key":"3078_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241914815","volume":"24","author":"J Lu","year":"2023","unstructured":"Lu J, Kornmann M, Traub B. Role of epithelial to mesenchymal transition in colorectal cancer. Int J Mol Sci. 2023;24:14815.","journal-title":"Int J Mol Sci"},{"key":"3078_CR37","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15785","volume":"8","author":"A Hagenkort","year":"2017","unstructured":"Hagenkort A, Paulin CB, Desroses M, Sarno A, Wiita E, Mortusewicz O, et al. dUTPase inhibition augments replication defects of 5-Fluorouracil. Oncotarget. 2017;8:23713.","journal-title":"Oncotarget"},{"key":"3078_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310687","volume":"24","author":"KK Lim","year":"2023","unstructured":"Lim KK, Koh NZH, Zeng YB, Chuan JK, Raechell R, Chen ES. Resistance to chemotherapeutic 5-fluorouracil conferred by modulation of heterochromatic integrity through Ino80 function in fission yeast. Int J Mol Sci. 2023;24:10687.","journal-title":"Int J Mol Sci"},{"key":"3078_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19173-2","volume":"11","author":"Y-H Cho","year":"2020","unstructured":"Cho Y-H, Ro EJ, Yoon J-S, Mizutani T, Kang D-W, Park J-C, et al. 5-FU promotes stemness of colorectal cancer via p53-mediated WNT\/\u03b2-catenin pathway activation. Nat Commun. 2020;11:5321.","journal-title":"Nat Commun"},{"key":"3078_CR40","doi-asserted-by":"publisher","first-page":"7","DOI":"10.13005\/bpj\/1608","volume":"12","author":"SA Aldossary","year":"2019","unstructured":"Aldossary SA. Review on pharmacology of cisplatin: clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J. 2019;12:7\u201315.","journal-title":"Biomed Pharmacol J"},{"key":"3078_CR41","doi-asserted-by":"publisher","first-page":"659","DOI":"10.3390\/cells12040659","volume":"12","author":"M Kciuk","year":"2023","unstructured":"Kciuk M, Gieleci\u0144ska A, Mujwar S, Ko\u0142at D, Ka\u0142uzi\u0144ska-Ko\u0142at \u017b, Celik I, et al. Doxorubicin\u2014an agent with multiple mechanisms of anticancer activity. Cells. 2023;12:659.","journal-title":"Cells"},{"key":"3078_CR42","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s12885-021-07845-1","volume":"21","author":"Y Xi","year":"2021","unstructured":"Xi Y, Jing Z, Wei W, Chun Z, Quan Q, Qing Z, et al. Inhibitory effect of sodium butyrate on colorectal cancer cells and construction of the related molecular network. BMC Cancer. 2021;21:127. https:\/\/doi.org\/10.1186\/s12885-021-07845-1.","journal-title":"BMC Cancer"},{"key":"3078_CR43","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.ejps.2019.04.011","volume":"134","author":"NM Kocaturk","year":"2019","unstructured":"Kocaturk NM, Akkoc Y, Kig C, Bayraktar O, Gozuacik D, Kutlu OJ. Autophagy as a molecular target for cancer treatment. Eur J Pharm Sci. 2019;134:116\u201337.","journal-title":"Eur J Pharm Sci"},{"key":"3078_CR44","doi-asserted-by":"publisher","first-page":"3142","DOI":"10.1111\/cas.14532","volume":"111","author":"S Blondy","year":"2020","unstructured":"Blondy S, David V, Verdier M, Mathonnet M, Perraud A, Christou N. 5-fluorouracil resistance mechanisms in colorectal cancer: from classical pathways to promising processes. Cancer Sci. 2020;111:3142\u201354. https:\/\/doi.org\/10.1111\/cas.14532.","journal-title":"Cancer Sci"},{"key":"3078_CR45","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1007\/s12672-024-01163-1","volume":"15","author":"L Yan","year":"2024","unstructured":"Yan L, Shi J, Zhu J. Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions. Discover Oncol. 2024;15:294. https:\/\/doi.org\/10.1007\/s12672-024-01163-1.","journal-title":"Discover Oncol"},{"key":"3078_CR46","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.devcel.2018.05.027","volume":"45","author":"NM Aiello","year":"2018","unstructured":"Aiello NM, Maddipati R, Norgard RJ, Balli D, Li J, Yuan S, et al. EMT subtype influences epithelial plasticity and mode of cell migration. Dev Cell. 2018;45:681-695.e4. https:\/\/doi.org\/10.1016\/j.devcel.2018.05.027.","journal-title":"Dev Cell"},{"key":"3078_CR47","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s12935-025-03758-2","volume":"25","author":"A Babajnai","year":"2025","unstructured":"Babajnai A, Rahmani S, Asadi MJ, Gheytanchi E, Adibhesami G, Vakhshiteh F, et al. Molecular and phenotypic characterization of 5-FU resistant colorectal cancer cells: toward enrichment of cancer stem cells. Cancer Cell Int. 2025;25:154. https:\/\/doi.org\/10.1186\/s12935-025-03758-2.","journal-title":"Cancer Cell Int"},{"key":"3078_CR48","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/tpj.2014.45","volume":"15","author":"Y Zheng","year":"2015","unstructured":"Zheng Y, Zhou J, Tong Y. Gene signatures of drug resistance predict patient survival in colorectal cancer. Pharmacogenomics J. 2015;15:135\u201343. https:\/\/doi.org\/10.1038\/tpj.2014.45.","journal-title":"Pharmacogenomics J"},{"key":"3078_CR49","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1074\/jbc.REV119.007759","volume":"295","author":"M Janiszewska","year":"2020","unstructured":"Janiszewska M, Primi MC, Izard T. Cell adhesion in cancer: beyond the migration of single cells. J Biol Chem. 2020;295:2495\u2013505. https:\/\/doi.org\/10.1074\/jbc.REV119.007759.","journal-title":"J Biol Chem"},{"key":"3078_CR50","doi-asserted-by":"publisher","first-page":"41706","DOI":"10.18632\/oncotarget.5991","volume":"6","author":"C Denise","year":"2015","unstructured":"Denise C, Paoli P, Calvani M, Taddei ML, Giannoni E, Kopetz S, et al. 5-fluorouracil resistant colon cancer cells are addicted to OXPHOS to survive and enhance stem-like traits. Oncotarget. 2015;6:41706.","journal-title":"Oncotarget"},{"key":"3078_CR51","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1093\/carcin\/bgv006","volume":"36","author":"S Toden","year":"2015","unstructured":"Toden S, Okugawa Y, Jascur T, Wodarz D, Komarova NL, Buhrmann C, et al. Curcumin mediates chemosensitization to 5-fluorouracil through miRNA-induced suppression of epithelial-to-mesenchymal transition in chemoresistant colorectal cancer. Carcinogenesis. 2015;36:355\u201367. https:\/\/doi.org\/10.1093\/carcin\/bgv006.","journal-title":"Carcinogenesis"},{"key":"3078_CR52","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12032-022-01864-z","volume":"40","author":"A Kumar","year":"2022","unstructured":"Kumar A, Singh AK, Singh H, Thareja S, Kumar P. Regulation of thymidylate synthase: an approach to overcome 5-FU resistance in colorectal cancer. Med Oncol. 2022;40:3. https:\/\/doi.org\/10.1007\/s12032-022-01864-z.","journal-title":"Med Oncol"},{"key":"3078_CR53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1561560","author":"B Huang","year":"2025","unstructured":"Huang B, Yuan Q, Sun J, Wang C, Yang D. Thymidine phosphorylase in nucleotide metabolism: physiological functions and its implications in tumorigenesis and anti-cancer therapy. Front Immunol. 2025. https:\/\/doi.org\/10.3389\/fimmu.2025.1561560.","journal-title":"Front Immunol"},{"key":"3078_CR54","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/ni.1674","volume":"10","author":"X Yu","year":"2009","unstructured":"Yu X, Harden K, Gonzalez CL, Francesco M, Chiang E, Irving B, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nature Immunol. 2009;10:48\u201357. https:\/\/doi.org\/10.1038\/ni.1674.","journal-title":"Nature Immunol"},{"key":"3078_CR55","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.molimm.2019.11.008","volume":"118","author":"D Anestakis","year":"2020","unstructured":"Anestakis D, Petanidis S, Domvri K, Tsavlis D, Zarogoulidis P, Katopodi T. Carboplatin chemoresistance is associated with CD11b+\/Ly6C+ myeloid release and upregulation of TIGIT and LAG3\/CD160 exhausted T cells. Mol Immunol. 2020;118:99\u2013109. https:\/\/doi.org\/10.1016\/j.molimm.2019.11.008.","journal-title":"Mol Immunol"},{"key":"3078_CR56","doi-asserted-by":"publisher","first-page":"691","DOI":"10.2174\/1566524021666211027090515","volume":"22","author":"S Taghvimi","year":"2022","unstructured":"Taghvimi S, Abbaszadeh S, Banan FB, Fard ES, Jamali Z, Najafabadi MA, et al. LncRNAs roles in chemoresistance of cancer cells. Curr Mol Med. 2022;22:691\u2013702.","journal-title":"Curr Mol Med"},{"key":"3078_CR57","doi-asserted-by":"publisher","first-page":"e923491","DOI":"10.12659\/MSM.923491","volume":"26","author":"G Guan","year":"2020","unstructured":"Guan G, Niu X, Qiao X, Wang X, Liu J, Zhong M. Upregulation of neural cell adhesion molecule 1 (NCAM1) by hsa-miR-141\u20133p suppresses ameloblastoma cell migration. Med Sci Monitor: Int Med J Exp Clin Res. 2020;26:e923491-1.","journal-title":"Med Sci Monitor: Int Med J Exp Clin Res"},{"key":"3078_CR58","doi-asserted-by":"publisher","first-page":"2650","DOI":"10.1111\/cas.15770","volume":"114","author":"L Zhao","year":"2023","unstructured":"Zhao L, Wu X, Zhang Z, Fang L, Yang B, Li Y. ELF1 suppresses autophagy to reduce cisplatin resistance via the miR-152-3p\/NCAM1\/ERK axis in lung cancer cells. Cancer Sci. 2023;114:2650\u201363. https:\/\/doi.org\/10.1111\/cas.15770.","journal-title":"Cancer Sci"},{"key":"3078_CR59","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25136853","volume":"25","author":"S Foutadakis","year":"2024","unstructured":"Foutadakis S, Kordias D, Vatsellas G, Magklara A. Identification of new chemoresistance-associated genes in triple-negative breast cancer by single-cell transcriptomic analysis. Int J Mol Sci. 2024;25:6853.","journal-title":"Int J Mol Sci"},{"key":"3078_CR60","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.951864","author":"X Zhou","year":"2022","unstructured":"Zhou X, Ao X, Jia Z, Li Y, Kuang S, Du C, et al. Non-coding RNA in cancer drug resistance: underlying mechanisms and clinical applications. Front Oncol. 2022. https:\/\/doi.org\/10.3389\/fonc.2022.951864.","journal-title":"Front Oncol"},{"key":"3078_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0776-6","volume":"9","author":"Q Wang","year":"2018","unstructured":"Wang Q, Shi Y-l, Zhou K, Wang L-l, Yan Z-x, Liu Y-l, et al. Pik3ca mutations confer resistance to first-line chemotherapy in colorectal cancer. Cell Death Dis. 2018;9:739. https:\/\/doi.org\/10.1038\/s41419-018-0776-6.","journal-title":"Cell Death Dis"},{"key":"3078_CR62","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13046-021-02229-6","volume":"41","author":"S Dong","year":"2022","unstructured":"Dong S, Liang S, Cheng Z, Zhang X, Luo L, Li L, et al. ROS\/PI3K\/Akt and Wnt\/\u03b2-catenin signalings activate HIF-1\u03b1-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer. J Exp Clin Cancer Res. 2022;41:15. https:\/\/doi.org\/10.1186\/s13046-021-02229-6.","journal-title":"J Exp Clin Cancer Res"},{"key":"3078_CR63","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1080\/14728222.2023.2218613","volume":"27","author":"S Halder","year":"2023","unstructured":"Halder S, Basu S, Lall SP, Ganti AK, Batra SK, Seshacharyulu P. Targeting the EGFR signaling pathway in cancer therapy: What\u2019s new in 2023? Expert Opin Therapeutic Targets. 2023;27:305\u201324.","journal-title":"Expert Opin Therapeutic Targets"},{"key":"3078_CR64","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.446","volume":"4","author":"N Zhang","year":"2023","unstructured":"Zhang N, Li Y. Receptor tyrosine kinases: biological functions and anticancer targeted therapy. MedComm. 2023;4:e446. https:\/\/doi.org\/10.1002\/mco2.446.","journal-title":"MedComm"},{"key":"3078_CR65","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S278013","author":"Y Lin","year":"2020","unstructured":"Lin Y, He Z, Ye J, Liu Z, She X, Gao X, et al. Progress in understanding the IL-6\/STAT3 pathway in colorectal cancer. OncoTargets and Therapy. 2020. https:\/\/doi.org\/10.2147\/OTT.S278013.","journal-title":"OncoTargets and Therapy"},{"key":"3078_CR66","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V122.21.1758.1758","volume":"122","author":"Q Cai","year":"2013","unstructured":"Cai Q, Huang H-q, Bai B, Lin S, Gao Y, Xia Y, et al. IL-6 promotes cell proliferation and antiapoptosis through activation of the JAK\/STAT3 pathway in patients with NK\/T - cell lymphoma and correlates with poor treatmemt outcome. Blood. 2013;122:1758\u20131758. https:\/\/doi.org\/10.1182\/blood.V122.21.1758.1758.","journal-title":"Blood"},{"key":"3078_CR67","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1111\/cas.12478","volume":"105","author":"HQ Yan","year":"2014","unstructured":"Yan HQ, Huang XB, Ke SZ, Jiang YN, Zhang YH, Wang YN, et al. Interleukin 6 augments lung cancer chemotherapeutic resistance via ataxia-telangiectasia mutated\/NF-kappaB pathway activation. Cancer Sci. 2014;105:1220\u20137. https:\/\/doi.org\/10.1111\/cas.12478.","journal-title":"Cancer Sci"},{"key":"3078_CR68","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.7150\/jca.47032","volume":"12","author":"H Wang","year":"2021","unstructured":"Wang H, Ren R, Yang Z, Cai J, Du S, Shen X. The COL11A1\/Akt\/CREB signaling axis enables mitochondrial-mediated apoptotic evasion to promote chemoresistance in pancreatic cancer cells through modulating BAX\/BCL-2 function. J Cancer. 2021;12:1406\u201320. https:\/\/doi.org\/10.7150\/jca.47032.","journal-title":"J Cancer"},{"key":"3078_CR69","first-page":"1631","volume":"36","author":"MI Koerber","year":"2016","unstructured":"Koerber MI, Staribacher A, Ratzenb\u00f6ck I, Steger G, Mader RM. NF\u03baB-associated pathways in progression of chemoresistance to 5-fluorouracil in an in vitro model of colonic carcinoma. Anticancer Res. 2016;36:1631\u20139.","journal-title":"Anticancer Res"},{"key":"3078_CR70","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41392-025-02176-0","volume":"10","author":"M Vogler","year":"2025","unstructured":"Vogler M, Braun Y, Smith VM, Westhoff M-A, Pereira RS, Pieper NM, et al. The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy. Signal Transduct Target Ther. 2025;10:91. https:\/\/doi.org\/10.1038\/s41392-025-02176-0.","journal-title":"Signal Transduct Target Ther"},{"key":"3078_CR71","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.jss.2003.08.103","volume":"114","author":"MM Mortenson","year":"2003","unstructured":"Mortenson MM, Schlieman MG, Virudalchalam S, Bold RJ. Overexpression of BCL-2 results in activation of the AKT\/NF-kB cell survival pathway. J Surg Res. 2003;114:302. https:\/\/doi.org\/10.1016\/j.jss.2003.08.103.","journal-title":"J Surg Res"}],"container-title":["Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-03078-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12032-025-03078-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-03078-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:18:53Z","timestamp":1762424333000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12032-025-03078-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":71,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["3078"],"URL":"https:\/\/doi.org\/10.1007\/s12032-025-03078-5","relation":{},"ISSN":["1559-131X"],"issn-type":[{"type":"electronic","value":"1559-131X"}],"subject":[],"published":{"date-parts":[[2025,10,10]]},"assertion":[{"value":"30 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 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":"Conflict of interest"}}],"article-number":"512"}}