Therapeutic Redox Reprogramming in Breast Cancer: From Antioxidant Modulation to Precision Nanomedicine.
8 affiliations
- 1Nanobiomedicine/Molecular and Cellular Oncology, ENT, University Medical Center Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany.
- 2Laboratory of Plant Cytoprotectors, Institute of Bioorganic Chemistry Named After A. Sadykov, Mirzo Ulugbek, 83, Tashkent 100125, Uzbekistan.
- 3Department of Environmental Engineering, Faculty of Engineering, Kyrgyz-Turkish Manas University, Bishkek 720038, Kyrgyzstan.
- 4Department of Engineering Fundamental Sciences, Faculty of Engineering, Artvin Çoruh University, Artvin 08000, Türkiye.
- 5Medicinal-Aromatic Plants Application and Research Center, Artvin Çoruh University, Artvin 08000, Türkiye.
- 6Department of Pharmacy Services, Vocational School, İstanbul Beykent University, Istanbul 34500, Türkiye.
- 7Faculty of Arts and Science, Chemistry Department, Aksaray University, Aksaray 68100, Türkiye.
- 8Vocational School of Health Science, Pharmacy Services Program, Tarsus University, Tarsus 33400, Türkiye.
Abstract
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.
Related
- State-matched redox nanomedicine for cell fate control and multicompartment therapeutic windows.
- Histone modifications in laryngeal squamous cell carcinoma: from epigenetic reprogramming to precision therapy
- Biochemical Characteristics of the Vascular Microenvironment in Pathological Conditions and Precision Therapeutic Strategies
- Gut microbiota modulation of gastrointestinal cancers: from dysbiosis signatures to therapeutic interventions
- Salidroside Regulates Energy Metabolism Reprogramming to Suppress Tumor Proliferation: Mechanisms and Therapeutic Implications
BibTeX
@article{kummer2026therapeutic,
title = {{Therapeutic Redox Reprogramming in Breast Cancer: From Antioxidant Modulation to Precision Nanomedicine.}},
author = {Nina Kummer and Sabina Gayibova and Takhir Aripov and Désirée Gül and Mustafa Dolaz and Burcu Önal Acet and Leyla Polat Köse and Mehmet Odabaşı and Roland H Stauber and Ömür Acet},
journal = {Antioxidants (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/antiox15101307},
url = {https://europepmc.org/article/MED/42939881},
note = {CC BY},
}
RIS
TY - JOUR
TI - Therapeutic Redox Reprogramming in Breast Cancer: From Antioxidant Modulation to Precision Nanomedicine.
AU - Nina Kummer
AU - Sabina Gayibova
AU - Takhir Aripov
AU - Désirée Gül
AU - Mustafa Dolaz
AU - Burcu Önal Acet
AU - Leyla Polat Köse
AU - Mehmet Odabaşı
AU - Roland H Stauber
AU - Ömür Acet
PY - 2026
DA - 2026/10/10
JO - Antioxidants (Basel, Switzerland)
DO - 10.3390/antiox15101307
UR - https://europepmc.org/article/MED/42939881
AB - 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.
SN - 2076-3921
ER -