Comprehensive Mechanistic Mapping of ROS Driven Oncolysis for Precision Therapeutics
Archives of Advances in Biosciences,
Vol. 17 No. 1 (2026),
28 Ordibehesht 2026
,
Page 1-19
https://doi.org/10.22037/aab.v17i1.51392
Abstract
Contex: Reactive oxygen species (ROS) have a contradictory function in cancer biology because they promote both oncogenic signaling and mediate cell death. At the molecular level, ROS consist of free radicals like O2•⁻, •OH and ONOO-, as well as non-radical oxidants like H2O2 and 1O2. Cytochrome P450 uncoupling, xanthine oxidase, ER oxidative protein folding (Ero1–PDI), peroxisomal β-oxidation, mitochondrial leakage (Complexes I/III), and NADPH oxidases (NOX1–5, DUOX1–2) are mechanisms that naturally produce these species. Exogenous stimuli such as photodynamic treatment, radiation, and nanoparticle-induced redox cycling further increase oxidative flux. In order to adapt, cancer cells reorganize redox homeostasis by upregulating SOD2, while glutathione peroxidases (GPX4), catalase, peroxiredoxins, and thiol buffers (GSH, thioredoxin) detoxify peroxides and maintain cysteine residues in a reduced form. Since Nrf2 hyperactivation encourages the long-term transcription of cytoprotective enzymes, the Nrf2-Keap1 axis is crucial to this network. Such hypertrophied antioxidant defenses establish a "redox setpoint" by keeping ROS levels below fatal thresholds but high enough to sustain oncogenic signaling via MAPK/ERK, JAK/STAT, NF-κB, and stability of HIF-1α.
Evidence Acquisition: A systematic search of major electronic databases was conducted through 2025 using redox-related keywords. Relevant peer-reviewed articles were selected and synthesized to evaluate ROS mechanisms and their therapeutic potential in oncology. The search integrated databases such as PubMed and Scopus, utilizing specific terms like Redox Homeostasis and Ferroptosis to ensure a comprehensive evaluation of current therapeutic vulnerabilities.
Results: The analysis highlights broad clinical applications in early cancer detection (skin, gastrointestinal, respiratory, cervical, and other organs), non-cancerous diseases (inflammation, infection, wound monitoring), and intraoperative guidance. Despite advantages like non-invasiveness and real-time diagnosis, limitations such as limited light penetration depth, complexity of data interpretation, and the inability to fully replace histopathology remain significant challenges.
Conclusion: Additional ROS amplification overwhelms defenses when GPX4 and GSH are reduced, leading to ferroptosis via lipid peroxidation, cytochrome c release, caspase activation, or mitochondrial permeability transition. A "redox vulnerability" is created as a result, which may be used therapeutically In parallel, ROS-induced DNA damages (such as 8-oxoG) activate ATM/ATR pathways, and ER stress initiates CHOP-mediated apoptosis. Crucially, immunogenic cell death brought on by oxidative damage can also release DAMPs including ATP, HMGB1, and calreticulin to boost antitumor immunity. Through the combination of redox buffering systems, antioxidant adaptations, and molecular-level ROS formation, this review reframes ROS as a biochemical language and therapeutic lever in oncology.
- ROS
- Redox setpoint
- Redox Vulnerability
- photodynamic therapy
- Apoptosis
- Ferroptosis
How to Cite
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