{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:49:34Z","timestamp":1782859774805,"version":"3.54.5"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s11033-026-12207-w","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:01:48Z","timestamp":1782856908000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of metformin-based chemo-radiotherapeutic strategies on breast cancer stemness and autophagy-associated gene expression: evidence from ALDH1A1 and LC3 expression analysis"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0462-0567","authenticated-orcid":false,"given":"Manal Lafta","family":"Abdulhassn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"issue":"3","key":"12207_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209\u2013249","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"12207_CR2","first-page":"17","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel RL, Miller KD, Wagle NS, Jemal A (2023) Cancer statistics, 2023. CA Cancer J Clin 73(1):17\u201348","journal-title":"CA Cancer J Clin"},{"issue":"10","key":"12207_CR3","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1038\/nm.4409","volume":"23","author":"E Batlle","year":"2017","unstructured":"Batlle E, Clevers H (2017) Cancer stem cells revisited. Nat Med 23(10):1124\u20131134","journal-title":"Nat Med"},{"key":"12207_CR4","doi-asserted-by":"publisher","first-page":"5416923","DOI":"10.1155\/2018\/5416923","volume":"2018","author":"LTH Phi","year":"2018","unstructured":"Phi LTH, Sari IN, Yang YG, Lee SH, Jun N, Kim KS et al (2018) Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int 2018:5416923","journal-title":"Stem Cells Int"},{"issue":"8","key":"12207_CR5","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.3390\/cells9081896","volume":"9","author":"K Dzobo","year":"2020","unstructured":"Dzobo K, Senthebane DA, Ganz C, Thomford NE, Wonkam A, Dandara C (2020) Advances in therapeutic targeting of cancer stem cells within the tumor microenvironment: an updated review. Cells 9(8):1896","journal-title":"Cells"},{"issue":"10","key":"12207_CR6","doi-asserted-by":"publisher","first-page":"11018","DOI":"10.18632\/oncotarget.6920","volume":"7","author":"H Tomita","year":"2016","unstructured":"Tomita H, Tanaka K, Tanaka T, Hara A (2016) Aldehyde dehydrogenase 1A1 in stem cells and cancer. Oncotarget 7(10):11018\u201311032","journal-title":"Oncotarget"},{"issue":"5","key":"12207_CR7","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.stem.2007.08.014","volume":"1","author":"C Ginestier","year":"2007","unstructured":"Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555\u2013567","journal-title":"Cell Stem Cell"},{"key":"12207_CR8","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1186\/1471-2407-14-444","volume":"14","author":"Y Liu","year":"2014","unstructured":"Liu Y, Lv DL, Duan JJ, Xu SL, Zhang JF, Yang XJ et al (2014) ALDH1A1 expression correlates with clinicopathologic features and poor prognosis of breast cancer patients: a systematic review and meta-analysis. BMC Cancer 14:444","journal-title":"BMC Cancer"},{"key":"12207_CR9","doi-asserted-by":"publisher","first-page":"3904645","DOI":"10.1155\/2019\/3904645","volume":"2019","author":"G Vassalli","year":"2019","unstructured":"Vassalli G (2019) Aldehyde dehydrogenases: not just markers, but functional regulators of stem cells. Stem Cells Int 2019:3904645","journal-title":"Stem Cells Int"},{"issue":"16","key":"12207_CR10","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1056\/NEJMra2022774","volume":"383","author":"N Mizushima","year":"2020","unstructured":"Mizushima N, Levine B (2020) Autophagy in human diseases. N Engl J Med 383(16):1564\u20131576","journal-title":"N Engl J Med"},{"issue":"9","key":"12207_CR11","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nrc.2017.53","volume":"17","author":"JMM Levy","year":"2017","unstructured":"Levy JMM, Towers CG, Thorburn A (2017) Targeting autophagy in cancer. Nat Rev Cancer 17(9):528\u2013542","journal-title":"Nat Rev Cancer"},{"key":"12207_CR12","doi-asserted-by":"crossref","unstructured":"Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S et al (2021) Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. ;17(1):1-382","DOI":"10.1080\/15548627.2020.1797280"},{"issue":"11","key":"12207_CR13","doi-asserted-by":"publisher","first-page":"3466","DOI":"10.3390\/ijms19113466","volume":"19","author":"CW Yun","year":"2018","unstructured":"Yun CW, Lee SH (2018) The roles of autophagy in cancer. Int J Mol Sci 19(11):3466","journal-title":"Int J Mol Sci"},{"issue":"10","key":"12207_CR14","first-page":"633","volume":"19","author":"M Foretz","year":"2023","unstructured":"Foretz M, Guigas B, Viollet B (2023) Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol 19(10):633\u2013654","journal-title":"Nat Rev Endocrinol"},{"issue":"9","key":"12207_CR15","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1158\/1940-6207.CAPR-13-0424","volume":"7","author":"S Gandini","year":"2014","unstructured":"Gandini S, Puntoni M, Heckman-Stoddard BM, Dunn BK, Ford L, DeCensi A et al (2014) Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res (Phila) 7(9):867\u2013885","journal-title":"Cancer Prev Res (Phila)"},{"issue":"5","key":"12207_CR16","first-page":"e612","volume":"26","author":"IC Lega","year":"2019","unstructured":"Lega IC, Fung K, Austin PC, Lipscombe LL (2019) Metformin and breast cancer stage at diagnosis: a population-based study. Curr Oncol 26(5):e612\u2013e617","journal-title":"Curr Oncol"},{"issue":"6","key":"12207_CR17","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3816\/CBC.2008.n.060","volume":"8","author":"PJ Goodwin","year":"2008","unstructured":"Goodwin PJ, Pritchard KI, Ennis M, Clemons M, Graham M, Fantus IG (2008) Insulin-lowering effects of metformin in women with early breast cancer. Clin Breast Cancer 8(6):501\u2013505","journal-title":"Clin Breast Cancer"},{"issue":"3","key":"12207_CR18","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.tcb.2015.10.013","volume":"26","author":"DG Hardie","year":"2016","unstructured":"Hardie DG, Schaffer BE, Brunet A (2016) AMPK: an energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol 26(3):190\u2013201","journal-title":"Trends Cell Biol"},{"issue":"3","key":"12207_CR19","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nrendo.2013.256","volume":"10","author":"I Pernicova","year":"2014","unstructured":"Pernicova I, Korbonits M (2014) Metformin\u2014mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol 10(3):143\u2013156","journal-title":"Nat Rev Endocrinol"},{"issue":"4","key":"12207_CR20","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.molcel.2018.07.030","volume":"71","author":"JH Cha","year":"2018","unstructured":"Cha JH, Yang WH, Xia W, Wei Y, Chan LC, Lim SO et al (2018) Metformin promotes antitumor immunity via endoplasmic-reticulum-associated degradation of PD-L1. Mol Cell 71(4):606\u2013620","journal-title":"Mol Cell"},{"issue":"2","key":"12207_CR21","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1093\/abbs\/gmx106","volume":"50","author":"N Saini","year":"2018","unstructured":"Saini N, Yang X (2018) Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem cells. Acta Biochim Biophys Sin (Shanghai) 50(2):133\u2013143","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"12207_CR22","first-page":"110146","volume":"366","author":"S Morab","year":"2022","unstructured":"Morab S, Mishra M, Barik M, Pradhan S, Parida S, Sahu M et al (2022) Aldehyde dehydrogenase 1A1 (ALDH1A1): friend or foe? Chem Biol Interact 366:110146","journal-title":"Chem Biol Interact"},{"issue":"6","key":"12207_CR23","doi-asserted-by":"publisher","first-page":"532","DOI":"10.3390\/cells8060532","volume":"8","author":"V Condelli","year":"2019","unstructured":"Condelli V, Crispo F, Pietrafesa M, Lettini G, Matassa DS, Esposito F et al (2019) HSP90 molecular chaperones, metabolic rewiring, and epigenetics: impact on tumor progression and perspective for anticancer therapy. Cells 8(6):532","journal-title":"Cells"},{"issue":"1","key":"12207_CR24","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1038\/s41598-019-38943-7","volume":"9","author":"B Toledo","year":"2019","unstructured":"Toledo B, Pijuan J, Mart\u00ednez-Barriocanal \u00c1, Rosell R, Korman AJ, Vaquero EC et al (2019) Metformin targets cancer stem cells and enhances the cytotoxic effect of chemotherapy in non-small cell lung cancer. Sci Rep 9(1):2392","journal-title":"Sci Rep"},{"key":"12207_CR25","first-page":"4101373","volume":"2020","author":"Q Zhang","year":"2020","unstructured":"Zhang Q, Xu X, Jiang M, Wang X, Jiang Y, Liu J (2020) Metformin suppresses DNA repair and sensitizes triple negative breast cancer cells to radiotherapy. Biomed Res Int 2020:4101373","journal-title":"Biomed Res Int"},{"issue":"1\u20132","key":"12207_CR26","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","volume":"176","author":"B Levine","year":"2019","unstructured":"Levine B, Kroemer G (2019) Biological functions of autophagy genes: a disease perspective. Cell 176(1\u20132):11\u201342","journal-title":"Cell"},{"issue":"16","key":"12207_CR27","doi-asserted-by":"publisher","first-page":"3307","DOI":"10.1002\/cncr.31335","volume":"124","author":"AV Onorati","year":"2018","unstructured":"Onorati AV, Dyczynski M, Ojha R, Amaravadi RK (2018) Targeting autophagy in cancer. Cancer 124(16):3307\u20133318","journal-title":"Cancer"},{"issue":"10","key":"12207_CR28","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.3390\/cancers11101599","volume":"11","author":"M P\u00e9rez-Hern\u00e1ndez","year":"2019","unstructured":"P\u00e9rez-Hern\u00e1ndez M, Arias A, Mart\u00ednez-Garc\u00eda D, P\u00e9rez-Tom\u00e1s R, Quesada R, Soto-Cerrato V (2019) Targeting autophagy for cancer treatment and tumor chemosensitization. Cancers (Basel) 11(10):1599","journal-title":"Cancers (Basel)"},{"issue":"2","key":"12207_CR29","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1158\/2159-8290.CD-18-0706","volume":"9","author":"VW Rebecca","year":"2019","unstructured":"Rebecca VW, Nicastri MC, Fennelly C, Chude CI, Barber-Rotenberg JS, Ronghe A et al (2019) PPT1 promotes tumor growth and is the molecular target of chloroquine derivatives in cancer. Cancer Discov 9(2):220\u2013229","journal-title":"Cancer Discov"},{"issue":"11\u201312","key":"12207_CR30","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1101\/gad.325514.119","volume":"33","author":"L Poillet-Perez","year":"2019","unstructured":"Poillet-Perez L, White E (2019) Role of tumor and host autophagy in cancer metabolism. Genes Dev 33(11\u201312):610\u2013619","journal-title":"Genes Dev"},{"issue":"13","key":"12207_CR31","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1200\/JCO.2016.69.7722","volume":"35","author":"A Sonnenblick","year":"2017","unstructured":"Sonnenblick A, Agbor-Tarh D, Bradbury I, Di Cosimo S, Azim HA Jr, Fumagalli D et al (2017) Impact of diabetes, insulin, and metformin use on the outcome of patients with human epidermal growth factor receptor 2-positive primary breast cancer: analysis from the ALTTO phase III randomized trial. J Clin Oncol 35(13):1421\u20131429","journal-title":"J Clin Oncol"},{"issue":"11","key":"12207_CR32","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1634\/theoncologist.2015-0096","volume":"20","author":"H Xu","year":"2015","unstructured":"Xu H, Chen K, Jia X, Tian Y, Dai Y, Li D et al (2015) Metformin use is associated with better survival of breast cancer patients with diabetes: a meta-analysis. Oncologist 20(11):1236\u20131244","journal-title":"Oncologist"},{"issue":"1","key":"12207_CR33","doi-asserted-by":"publisher","first-page":"7656","DOI":"10.1038\/s41598-022-11138-3","volume":"12","author":"HE Barakat","year":"2022","unstructured":"Barakat HE, Hussein RRS, Elberry AA, Zaki MA, Ramadan ME (2022) The impact of metformin use on the outcomes of locally advanced breast cancer patients receiving neoadjuvant chemotherapy: an open-labelled randomized controlled trial. Sci Rep 12(1):7656","journal-title":"Sci Rep"},{"issue":"7","key":"12207_CR34","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/onc.2017.367","volume":"37","author":"E Cuy\u00e0s","year":"2018","unstructured":"Cuy\u00e0s E, Fern\u00e1ndez-Arroyo S, Verdura S, Garc\u00eda R\u00c1, Stursa J, Werner L et al (2018) Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism. Oncogene 37(7):963\u2013970","journal-title":"Oncogene"},{"issue":"4","key":"12207_CR35","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1016\/j.bbrc.2015.07.117","volume":"464","author":"P Li","year":"2015","unstructured":"Li P, Zhao M, Parris AB, Feng X, Yang X (2015) p53 is required for metformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. Biochem Biophys Res Commun 464(4):1267\u20131274","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"12207_CR36","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1042\/BJ20140620","volume":"462","author":"HR Bridges","year":"2014","unstructured":"Bridges HR, Jones AJ, Pollak MN, Hirst J (2014) Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J 462(3):475\u2013487","journal-title":"Biochem J"},{"issue":"2","key":"12207_CR37","doi-asserted-by":"publisher","first-page":"81","DOI":"10.2165\/11534750-000000000-00000","volume":"50","author":"GG Graham","year":"2011","unstructured":"Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK et al (2011) Clinical pharmacokinetics of metformin. Clin Pharmacokinet 50(2):81\u201398","journal-title":"Clin Pharmacokinet"},{"issue":"20","key":"12207_CR38","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1001\/jama.2022.6147","volume":"327","author":"PJ Goodwin","year":"2022","unstructured":"Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J et al (2022) Effect of metformin vs placebo on invasive disease-free survival in patients with breast cancer: the MA.32 randomized clinical trial. JAMA 327(20):1963\u20131973","journal-title":"JAMA"},{"key":"12207_CR39","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.breast.2019.08.003","volume":"48","author":"I Pimentel","year":"2019","unstructured":"Pimentel I, Lohmann AE, Ennis M, Dowling RJ, Cescon D, Elser C et al (2019) A phase II randomized clinical trial of the effect of metformin versus placebo on progression-free survival in women with metastatic breast cancer receiving standard chemotherapy. Breast 48:17\u201323","journal-title":"Breast"},{"issue":"26","key":"12207_CR40","doi-asserted-by":"publisher","first-page":"40767","DOI":"10.18632\/oncotarget.8194","volume":"7","author":"YK Chae","year":"2016","unstructured":"Chae YK, Arya A, Malecek MK, Shin DS, Carneiro B, Chandra S et al (2016) Repurposing metformin for cancer treatment: current clinical studies. Oncotarget 7(26):40767\u201340780","journal-title":"Oncotarget"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-026-12207-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11033-026-12207-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-026-12207-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:01:56Z","timestamp":1782856916000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11033-026-12207-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["12207"],"URL":"https:\/\/doi.org\/10.1007\/s11033-026-12207-w","relation":{},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"1 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The Comparative Cross-Sectional Study was performed at the National Center for Educational Laboratories in Medical City, Iraq, from January 2025 to December 2025 and was approved by the Institutional Review Board (IRB) approval number: 1470 in accordance with the Declaration of Helsinki.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Due to the nature of the study and the use of anonymized data, the requirement for informed consent was waived by the Institutional Review Board.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}}],"article-number":"1033"}}