# Oxidative Stress and Inflammation in Colorectal Cancer–Redox–Immune Crosstalk, Biomarkers, and Translational Implications: A Qualitative Systematic Review

## TL;DR

This review explores how oxidative stress and inflammation work together in colorectal cancer, highlighting key pathways, potential biomarkers, and emerging treatment strategies.

## Contribution

The paper systematically reviews the redox-immune crosstalk in colorectal cancer and identifies novel biomarkers and therapeutic strategies with translational potential.

## Key findings

- Redox-sensitive pathways like NF-κB, NRF2, and IL-6/JAK/STAT3 are central to colorectal cancer progression and therapy resistance.
- Biomarkers such as 8-OHdG, MDA, and IL-6 are associated with tumor stage, prognosis, and treatment response.
- Combining redox-targeted therapies with immunotherapy or microbiota modulation shows promise in preclinical studies.

## Abstract

Oxidative stress and chronic inflammation cooperate to drive colorectal carcinogenesis, tumor progression, invasion, and therapy resistance.NF-κB, NRF2, and IL-6/JAK/STAT3 are central redox-sensitive signaling nodes with therapeutic relevance.Biomarkers (8-OHdG, MDA, F2-isoprostanes, CRP, IL-6, and TNF-α) may refine diagnosis, prognosis, and monitoring.Aspirin/COX-2 inhibition, antioxidants, and pathway modulators show preventive/adjunctive potential.Combinations with checkpoint inhibitors and microbiota modulation are emerging translational avenues.

Oxidative stress and chronic inflammation cooperate to drive colorectal carcinogenesis, tumor progression, invasion, and therapy resistance.

NF-κB, NRF2, and IL-6/JAK/STAT3 are central redox-sensitive signaling nodes with therapeutic relevance.

Biomarkers (8-OHdG, MDA, F2-isoprostanes, CRP, IL-6, and TNF-α) may refine diagnosis, prognosis, and monitoring.

Aspirin/COX-2 inhibition, antioxidants, and pathway modulators show preventive/adjunctive potential.

Combinations with checkpoint inhibitors and microbiota modulation are emerging translational avenues.

Oxidative stress and chronic inflammation are tightly interconnected biological processes that play central roles in colorectal cancer (CRC) initiation, progression, and resistance to therapy. Understanding their reciprocal interactions may identify novel biomarkers and therapeutic targets with translational relevance. Methods: This systematic review with qualitative synthesis was conducted in accordance with the PRISMA 2020 guidelines. A comprehensive literature search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar was performed from January 2005 to June 2025. Eligible studies investigated mechanistic links between oxidative stress and inflammation in colorectal cancer, assessed oxidative or inflammatory biomarkers, or explored redox- and inflammation-targeted therapeutic strategies. Study selection and data extraction were performed systematically. Due to heterogeneity in study designs and outcomes, a qualitative synthesis was undertaken without meta-analysis. Results: Twenty-six studies met the inclusion criteria. Evidence consistently demonstrated that redox-sensitive pathways—including NF-κB, NRF2, and IL-6/JAK/STAT3—drive colorectal carcinogenesis by promoting genomic instability, immune evasion, angiogenesis, and therapy resistance. Biomarkers such as 8-hydroxy-2′-deoxyguanosine, malondialdehyde, F2-isoprostanes, C-reactive protein, interleukin-6, and tumor necrosis factor-α were frequently associated with tumor stage, prognosis, and treatment response. Therapeutic strategies targeting oxidative stress and inflammation showed promising preclinical and early translational results, particularly in combination with chemotherapy or immunotherapy. Conclusion: Oxidative stress and inflammation constitute a synergistic axis that critically influences colorectal cancer biology. Although several biomarkers and redox-targeted interventions demonstrate translational potential, robust clinical validation is still required before routine implementation. Integrative strategies guided by biomarker profiling may represent a future direction for personalized CRC management. Most therapeutic approaches discussed are supported by preclinical and early translational evidence, and their clinical applicability remains to be validated.