{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:27:00Z","timestamp":1779100020417,"version":"3.51.4"},"reference-count":22,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T00:00:00Z","timestamp":1708819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-47\/2023-01\/200107"],"award-info":[{"award-number":["451-03-47\/2023-01\/200107"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-47\/2023-01\/200378"],"award-info":[{"award-number":["451-03-47\/2023-01\/200378"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-9\/2021-14\/200378"],"award-info":[{"award-number":["451-03-9\/2021-14\/200378"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 25\/19"],"award-info":[{"award-number":["JP 25\/19"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 05\/20"],"award-info":[{"award-number":["JP 05\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 06\/20"],"award-info":[{"award-number":["JP 06\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 24\/20"],"award-info":[{"award-number":["JP 24\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["952603 (SGABU)"],"award-info":[{"award-number":["952603 (SGABU)"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-47\/2023-01\/200107"],"award-info":[{"award-number":["451-03-47\/2023-01\/200107"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-47\/2023-01\/200378"],"award-info":[{"award-number":["451-03-47\/2023-01\/200378"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-9\/2021-14\/200378"],"award-info":[{"award-number":["451-03-9\/2021-14\/200378"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 25\/19"],"award-info":[{"award-number":["JP 25\/19"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 05\/20"],"award-info":[{"award-number":["JP 05\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 06\/20"],"award-info":[{"award-number":["JP 06\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 24\/20"],"award-info":[{"award-number":["JP 24\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["952603 (SGABU)"],"award-info":[{"award-number":["952603 (SGABU)"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-47\/2023-01\/200107"],"award-info":[{"award-number":["451-03-47\/2023-01\/200107"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-47\/2023-01\/200378"],"award-info":[{"award-number":["451-03-47\/2023-01\/200378"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-9\/2021-14\/200378"],"award-info":[{"award-number":["451-03-9\/2021-14\/200378"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 25\/19"],"award-info":[{"award-number":["JP 25\/19"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 05\/20"],"award-info":[{"award-number":["JP 05\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 06\/20"],"award-info":[{"award-number":["JP 06\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["JP 24\/20"],"award-info":[{"award-number":["JP 24\/20"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["952603 (SGABU)"],"award-info":[{"award-number":["952603 (SGABU)"]}]},{"name":"Junior projects of Faculty of Medical Sciences, University of Kragujevac","award":["451-03-47\/2023-01\/200107"],"award-info":[{"award-number":["451-03-47\/2023-01\/200107"]}]},{"name":"Junior projects of Faculty of Medical Sciences, University of Kragujevac","award":["451-03-47\/2023-01\/200378"],"award-info":[{"award-number":["451-03-47\/2023-01\/200378"]}]},{"name":"Junior projects of Faculty of Medical Sciences, University of Kragujevac","award":["451-03-9\/2021-14\/200378"],"award-info":[{"award-number":["451-03-9\/2021-14\/200378"]}]},{"name":"Junior projects of Faculty of Medical Sciences, University of Kragujevac","award":["JP 25\/19"],"award-info":[{"award-number":["JP 25\/19"]}]},{"name":"Junior projects of Faculty of Medical Sciences, University of Kragujevac","award":["JP 05\/20"],"award-info":[{"award-number":["JP 05\/20"]}]},{"name":"Junior projects of Faculty of Medical Sciences, University of Kragujevac","award":["JP 06\/20"],"award-info":[{"award-number":["JP 06\/20"]}]},{"name":"Junior projects of Faculty of Medical Sciences, University of Kragujevac","award":["JP 24\/20"],"award-info":[{"award-number":["JP 24\/20"]}]},{"name":"Junior projects of Faculty of Medical Sciences, University of Kragujevac","award":["952603 (SGABU)"],"award-info":[{"award-number":["952603 (SGABU)"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["451-03-47\/2023-01\/200107"],"award-info":[{"award-number":["451-03-47\/2023-01\/200107"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["451-03-47\/2023-01\/200378"],"award-info":[{"award-number":["451-03-47\/2023-01\/200378"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["451-03-9\/2021-14\/200378"],"award-info":[{"award-number":["451-03-9\/2021-14\/200378"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["JP 25\/19"],"award-info":[{"award-number":["JP 25\/19"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["JP 05\/20"],"award-info":[{"award-number":["JP 05\/20"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["JP 06\/20"],"award-info":[{"award-number":["JP 06\/20"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["JP 24\/20"],"award-info":[{"award-number":["JP 24\/20"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["952603 (SGABU)"],"award-info":[{"award-number":["952603 (SGABU)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>(1) Background: Cancer stem cells (CSCs) are a subpopulation of cells in a tumor that can self-regenerate and produce different types of cells with the ability to initiate tumor growth and dissemination. Chemotherapy resistance, caused by numerous mechanisms by which tumor tissue manages to overcome the effects of drugs, remains the main problem in cancer treatment. The identification of markers on the cell surface specific to CSCs is important for understanding this phenomenon. (2) Methods: The expression of markers CD24, CD44, ALDH1, and ABCG2 was analyzed on the surface of CSCs in two cancer cell lines, MDA-MB-231 and HCT-116, after treatment with 5-fluorouracil (5-FU) using flow cytometry analysis. A machine learning model (ML)\u2013genetic algorithm (GA) was used for the in silico simulation of drug resistance. (3) Results: As evaluated through the use of flow cytometry, the percentage of CD24-CD44+ MDA-MB-231 and CD44, ALDH1 and ABCG2 HCT-116 in a group treated with 5-FU was significantly increased compared to untreated cells. The CSC population was enriched after treatment with chemotherapy, suggesting that these cells have enhanced drug resistance mechanisms. (4) Conclusions: Each individual GA prediction model achieved high accuracy in estimating the expression rate of CSC markers on cancer cells treated with 5-FU. Artificial intelligence can be used as a powerful tool for predicting drug resistance.<\/jats:p>","DOI":"10.3390\/curroncol31030091","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T11:31:21Z","timestamp":1708947081000},"page":"1221-1234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Modeling 5-FU-Induced Chemotherapy Selection of a Drug-Resistant Cancer Stem Cell Subpopulation"],"prefix":"10.3390","volume":"31","author":[{"given":"Amra","family":"Ramovi\u0107 Hamzagi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Medical Sciences, Department of Genetics, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Serbia for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7767-1345","authenticated-orcid":false,"given":"Danijela","family":"Cvetkovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Department of Genetics, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Serbia for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-9004","authenticated-orcid":false,"given":"Marina","family":"Gazdi\u0107 Jankovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Department of Genetics, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Serbia for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4518-1066","authenticated-orcid":false,"given":"Nevena","family":"Milivojevi\u0107 Dimitrijevi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Information Technologies Kragujevac, University of Kragujevac, Liceja Kne\u017eevine Srbije 1A, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-4586","authenticated-orcid":false,"given":"Dalibor","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"Institute for Information Technologies Kragujevac, University of Kragujevac, Liceja Kne\u017eevine Srbije 1A, 34000 Kragujevac, Serbia"},{"name":"Bioengineering Research and Development Center (BioIRC), Prvoslava Stojanovica 6, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8833-8035","authenticated-orcid":false,"given":"Marko","family":"\u017divanovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Information Technologies Kragujevac, University of Kragujevac, Liceja Kne\u017eevine Srbije 1A, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-7414","authenticated-orcid":false,"given":"Nikolina","family":"Kastratovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Department of Genetics, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Serbia for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2056-1158","authenticated-orcid":false,"given":"Ivica","family":"Petrovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Department of Pathophysiology, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Department of Genetics, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Serbia for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2003-8124","authenticated-orcid":false,"given":"Milena","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, University of Kragujevac, Radoja Domanovi\u0107a 12, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2093-5335","authenticated-orcid":false,"given":"Dragana","family":"\u0160ekli\u0107","sequence":"additional","affiliation":[{"name":"Institute for Information Technologies Kragujevac, University of Kragujevac, Liceja Kne\u017eevine Srbije 1A, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9964-5615","authenticated-orcid":false,"given":"Nenad","family":"Filipovi\u0107","sequence":"additional","affiliation":[{"name":"Bioengineering Research and Development Center (BioIRC), Prvoslava Stojanovica 6, 34000 Kragujevac, Serbia"},{"name":"Faculty of Engineering, University of Kragujevac, Sestre Janji\u0107 6, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-2720","authenticated-orcid":false,"given":"Biljana","family":"Ljuji\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Department of Genetics, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Serbia for Harm Reduction of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bukowski, K., Kciuk, M., and Kontek, R. (2020). Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093233"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13856","DOI":"10.1038\/s41598-017-14364-2","article-title":"Unraveling the roles of CD44\/CD24 and ALDH1 as cancer stem cell markers in tumorigenesis and metastasis","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_4","first-page":"e07273","article-title":"Biological characteristics of a sub-population of cancer stem cells from two triple-negative breast tumour cell lines","volume":"10","author":"Alfaro","year":"2021","journal-title":"Heliyon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ctrv.2018.07.004","article-title":"Cancer stem cell in breast cancer therapeutic resistance","volume":"69","author":"Bai","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sha, J., Bai, Y., Ngo, H.X., Okui, T., and Kanno, T. (2021). Overview of Evidence-Based Chemotherapy for Oral Cancer: Focus on Drug Resistance Related to the Epithelial-Mesenchymal Transition. Biomolecules, 16.","DOI":"10.3390\/biom11060893"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13287-022-02856-6","article-title":"Drug resistance in cancer therapy: The Pandora\u2019s Box of cancer stem cells","volume":"13","author":"Rezayatmand","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1093\/bib\/bbx065","article-title":"Mathematical modeling, and computational prediction of cancer drug resistance","volume":"19","author":"Sun","year":"2018","journal-title":"Brief. Bioinform."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12964-020-00627-5","article-title":"Drug resistance and Cancer stem cells","volume":"19","author":"Li","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/cts.12884","article-title":"Precision Medicine, AI, and the Future of Personalized Health Care","volume":"14","author":"Johnson","year":"2020","journal-title":"CTS-Clin. Transl. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12943-017-0600-4","article-title":"Intra-tumor heterogeneity from a cancer stem cell perspective","volume":"16","author":"Prasetyanti","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"813","DOI":"10.2217\/bmm-2017-0398","article-title":"Cancer stem cells in triple-negative breast cancer: A potential target and prognostic marker","volume":"12","author":"Chen","year":"2018","journal-title":"Biomark. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7657","DOI":"10.18632\/oncotarget.7084","article-title":"Role of CD44(high)\/CD133(high) HCT-116 cells in the tumorigenesis of colon cancer","volume":"7","author":"Zhou","year":"2016","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5458","DOI":"10.1002\/jcp.26406","article-title":"Oxaliplatin resistance in colorectal cancer cells is mediated via activation of ABCG2 to alleviate ER stress induced apoptosis","volume":"233","author":"Hsu","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8721","DOI":"10.7150\/thno.41648","article-title":"Stem cell programs in cancer initiation, progression, and therapy resistance","volume":"9","author":"Huang","year":"2020","journal-title":"Theranostics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/jcp.29044","article-title":"Cancer stem cells: A review from origin to therapeutic implications","volume":"235","author":"Atashzar","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s11030-021-10217-3","article-title":"Artificial intelligence to deep learning: Machine intelligence approach for drug discovery","volume":"25","author":"Gupta","year":"2021","journal-title":"Mol. Divers."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1016\/j.csbj.2021.07.003","article-title":"Machine learning in the prediction of cancer therapy","volume":"19","author":"Rafique","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"364","DOI":"10.2174\/1574892818666221018091415","article-title":"Prediction of Cancer Treatment Using Advancements in Machine Learning","volume":"18","author":"Ling","year":"2023","journal-title":"Recent Pat. Anti-Cancer Drug Discov."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"O\u2019Neill, M.R. (2009). Riccardo Poli, William B. Langdon, Nicholas F. McPhee: A Field Guide to Genetic Programming, Springer.","DOI":"10.1007\/s10710-008-9073-y"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"339","DOI":"10.15171\/apb.2017.041","article-title":"The different mechanisms of cancer drug resistance: A brief review","volume":"7","author":"Mansoori","year":"2017","journal-title":"Adv. Pharm. Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.3389\/fimmu.2020.01280","article-title":"Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies","volume":"11","author":"Walcher","year":"2020","journal-title":"Front. Immunol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/3\/91\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:04:30Z","timestamp":1760105070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/3\/91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,25]]},"references-count":22,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["curroncol31030091"],"URL":"https:\/\/doi.org\/10.3390\/curroncol31030091","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,25]]}}}