Therapeutic Redox Reprogramming in Breast Cancer: From Antioxidant Modulation to Precision Nanomedicine

Breast cancer progression and therapeutic resistance are closely associated with disrupted redox homeostasis, in which oxidative stress drives tumor growth, metabolic adaptation, and treatment failure. Although antioxidants have traditionally been considered cytoprotective agents, their effects on tumor redox signaling are highly context-dependent, creating an antioxidant paradox that limits their therapeutic application. This review examines how dysregulated redox signaling shapes breast cancer biology and therapeutic response across ER+, HER2+, and triple-negative subtypes, with emphasis on the NRF2–KEAP1, p53, PI3K/AKT, MAPK, and HIF-1α pathways. These mechanisms provide a biological rationale for selectively modulating tumor redox states rather than broadly suppressing oxidative stress. Within this framework, redox-responsive nanocarriers and nanozymes offer opportunities for precise spatial and temporal redox modulation, enhanced tumor targeting, and controlled therapeutic activity while potentially minimizing effects on healthy tissues. Redox-directed nanotherapeutics may also influence the tumor immune microenvironment, angiogenesis, and metabolic rewiring. However, clinical translation remains constrained by dose- and context-dependent effects, intratumoral heterogeneity, limited biomarker validation, and inadequate predictive models. Personalized redox nanomedicine integrating subtype-specific redox profiling, smart nanotherapeutic platforms, and biomarker-guided patient stratification could establish redox modulation as a precision therapeutic axis and improve treatment outcomes in breast cancer.

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