Abstract
Aim Recent studies reveal that hypoxia, oxidative stress, and impaired protein folding contribute to tumor development and breast cancer treatment resistance. Endoplasmic Reticulum Oxidoreductin 1 Alpha (ERO1α) regulates redox balance in the endoplasmic reticulum by reoxidizing protein disulfide isomerase, facilitating disulfide bond formation while generating reactive oxygen species. Elevated ERO1α levels are linked to tumor aggressiveness, metastasis, and poor outcomes. This systematic review aimed to critically analyze and summarize current research on ERO1α with a focus on breast cancer. Methods This review followed PRISMA 2020 guidelines. PubMed, Scopus, and ScienceDirect databases were searched up to May 31, 2025. Eligible studies included original in vitro and in vivo research on ERO1α in breast cancer. After screening and assessment, 11 articles met the inclusion criteria. Results ERO1α plays important roles in key cancer pathways including hypoxia response, angiogenesis, immune regulation, and ferroptosis resistance. It promotes angiogenesis via VEGF-A maturation and contributes to immune evasion by enhancing PD-L1 expression. Elevated ERO1α expression increases oxidative stress and supports tumor survival. Despite strong evidence of its tumor-promoting functions, no specific ERO1α inhibitors are currently approved for clinical use. Conclusion ERO1α is a critical regulator of redox homeostasis in breast cancer and contributes to tumor progression. Its involvement in angiogenesis, immune evasion, and stress adaptation highlights its potential as both a therapeutic target and a prognostic marker. Summarizing molecular mechanisms associated with ERO1α overexpression may guide future research and drug development targeting redox pathways in cancer.