Gastric Carcinogenesis and Underlying Molecular Mechanisms:Helicobacter pyloriand Novel Targeted Therapy

Abstract

The oxygen-derived free radicals that are released from activated neutrophils are one of the cytotoxic factors ofHelicobacter pylori-induced gastric mucosal injury. Increased cytidine deaminase activity inH. pylori-infected gastric tissues promotes the accumulation of various mutations and might promote gastric carcinogenesis. Cytotoxin-associated gene A (CagA) is delivered into gastric epithelial cells via bacterial type IV secretion system, and it causes inflammation and activation of oncogenic pathways.H. pyloriinfection induces epigenetic transformations, such as aberrant promoter methylation in tumor-suppressor genes. Aberrant expression of microRNAs is also reportedly linked to gastric tumorogenesis. Moreover, recent advances in molecular targeting therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER-2) therapies. This updated review article highlights possible mechanisms of gastric carcinogenesis includingH. pylori-associated factors.