Rethinking Oxidative Stress in Helicobacter pylori: A Multidisciplinary Framework Linking Redox Signaling, Cellular...

Area of Science:

• Gastroenterology and Oncology
• Cellular Biology
• Biochemistry

Background:

• Helicobacter pylori infection is a primary cause of gastric cancer, but the underlying biological mechanisms remain unclear.
• Existing reviews often focus narrowly on oxidative stress or specific virulence factors.
• A comprehensive understanding is needed to improve diagnosis and treatment strategies for H. pylori-associated gastric cancer.

Purpose of the Study:

• To synthesize current evidence into an integrated redox-centered framework for gastric carcinogenesis.
• To elucidate the roles of key signaling pathways in H. pylori-induced malignant transformation.
• To critically evaluate current diagnostic and therapeutic approaches and propose future directions.

Main Methods:

• Systematic review and synthesis of existing literature on H. pylori infection and gastric cancer.
• Integration of evidence on redox imbalance, signaling pathways, and epithelial adaptation.
• Conceptual modeling of disease progression and critical analysis of diagnostic/therapeutic strategies.

Main Results:

• Persistent redox imbalance interacts with inflammation, mitochondrial dysfunction, metabolic changes, epigenetics, microbiome, and oncogenic pathways.
• Key signaling pathways (NF-κB, STAT3, PI3K/AKT, HIF-1α, β-catenin, Hippo-YAP) are crucial for epithelial survival, inflammation, and transformation.
• A threshold model describes progression from epithelial stress to oncogenic reprogramming.

Conclusions:

• A redox-centered framework provides a multidimensional perspective on H. pylori-associated gastric carcinogenesis.
• Conventional diagnostics and therapies have limitations; emerging approaches offer improved risk stratification.
• Future strategies should focus on stage-specific, compartment-directed therapies, including selective redox modulation and precision targeting.