{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:22:29Z","timestamp":1792804949654,"version":"4.5.0"},"reference-count":59,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nazarbayev University Collaborative Research","award":["111024CRP2020"],"award-info":[{"award-number":["111024CRP2020"]}],"id":[{"id":"https:\/\/ror.org\/052bx8q98","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxia, oxidative stress, and impaired protein folding contribute to tumor progression and therapy resistance. Endoplasmic Reticulum Oxidoreductin 1 Alpha (ERO1\u03b1) is a key enzyme regulating redox homeostasis in the endoplasmic reticulum by reoxidizing protein disulfide isomerase, facilitating disulfide bond formation, and generating reactive oxygen species. Elevated ERO1\u03b1 levels are associated with increased tumor aggressiveness, metastasis, and poor clinical outcomes. Despite growing evidence of its tumor-promoting functions, no clinically approved ERO1\u03b1 inhibitors exist. This systematic review provides a comprehensive and integrative analysis of current research on ERO1\u03b1 in breast cancer, emphasizing its roles in hypoxia response, angiogenesis, immune modulation, and ferroptosis resistance. We discuss mechanistic links, including VEGF-A maturation and PD-L1-mediated immune evasion, and highlight recent advances in small-molecule ERO1\u03b1 inhibitors and preclinical therapeutic strategies. By consolidating molecular insights and translational considerations, this review underscores ERO1\u03b1 as both a promising therapeutic target and potential prognostic marker, offering guidance for future drug development and targeted interventions in redox-dependent cancer pathways.<\/jats:p>","DOI":"10.3390\/ijms262110276","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"10276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["ERO1\u03b1 as a Potential Drug Target for Breast Cancer: A Systematic Review of Current Evidence"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2019-4491","authenticated-orcid":false,"given":"Kamilla","family":"Khojayeva","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiman","family":"Moldasheva","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Aljofan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Drug Discovery and Development, Center of Life Sciences, National Laboratory, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.gendis.2018.05.001","article-title":"Breast Cancer Development and Progression: Risk Factors, Cancer Stem Cells, Signaling Pathways, Genomics, and Molecular Pathogenesis","volume":"5","author":"Feng","year":"2018","journal-title":"Genes Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Moura, T., Laranjeira, P., Caramelo, O., Gil, A.M., and Paiva, A. 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