Ozone therapy in colorectal cancer

Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality, and metastatic progression, recurrence, chemoresistance, and treatment-related toxicity continue to limit outcomes. Medical ozone has attracted interest as a potential adjunct because, after reacting with biological fluids, it generates short-lived redox mediators such as hydrogen peroxide and lipid oxidation products that may influence NRF2/Keap1, NF-κB, HIF-1α, mitochondrial apoptosis, cytokine signaling, and the tumor microenvironment. However, current CRC-specific evidence is limited and heterogeneous. Experimental studies using CRC cell lines and animal models suggest possible effects on apoptosis, oxidative stress, inflammatory modulation, hypoxia-related pathways, and chemosensitivity, but these findings remain preclinical and are not sufficient to establish antitumor efficacy. Clinical evidence in CRC patients is scarce and mainly relates to supportive care, including radiation-induced rectal injury, chronic treatment-related symptoms, and chemotherapy-induced peripheral neuropathy, rather than tumor response or survival. Importantly, ozone biology is context dependent: activation of adaptive antioxidant responses may protect normal tissues but could also enhance tumor cell stress tolerance under certain conditions. Route-specific safety is also critical, as inhaled ozone is toxic, whereas non-inhalational approaches require standardized dosing and monitoring. Overall, ozone therapy should be considered an investigational adjunct in CRC, with future studies requiring rigorous trial design, biomarker stratification, standardized administration protocols, and clear separation of anticancer endpoints from symptom-control outcomes.