ERO1α as a Potential Drug Target for Breast Cancer: A Systematic Review of Current Evidence

TL;DR

This review explores ERO1α's role in breast cancer progression and highlights its potential as a drug target for new therapies.

Contribution

The paper systematically reviews ERO1α's tumor-promoting functions and its potential as a novel therapeutic target in breast cancer.

Findings

ERO1α is linked to increased tumor aggressiveness and poor clinical outcomes in breast cancer.

ERO1α contributes to hypoxia response, angiogenesis, immune evasion, and resistance to ferroptosis.

Recent advances in ERO1α inhibitors show promise for preclinical therapeutic strategies.

Abstract

Hypoxia, oxidative stress, and impaired protein folding contribute to tumor progression and therapy resistance. Endoplasmic Reticulum Oxidoreductin 1 Alpha (ERO1α) 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 ERO1α levels are associated with increased tumor aggressiveness, metastasis, and poor clinical outcomes. Despite growing evidence of its tumor-promoting functions, no clinically approved ERO1α inhibitors exist. This systematic review provides a comprehensive and integrative analysis of current research on ERO1α 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 ERO1α inhibitors and preclinical therapeutic strategies. By consolidating molecular insights and translational considerations, this review underscores ERO1α as both a promising therapeutic target and potential prognostic marker, offering guidance for future drug development and targeted interventions in redox-dependent cancer pathways.

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