Molecular Pathways: The Complex Roles of Inflammation Pathways in the Development and Treatment of Liver Cancer

Inflammatory signals from the surrounding microenvironment play important roles in tumor promotion. Key inflammatory mediators and pathways that induce and sustain tumorigenesis have recently been identified in many different cancers. Hepatocellular carcinoma is a paradigm for inflammation-induced cancer, as it most frequently develops in the setting of chronic hepatitis, consecutive cellular damage, and compensatory regeneration. Recent studies revealed that liver damage-mediated inflammation and carcinogenesis are triggered by a complex cross-talk between NF-kappa B, c-jun-NH2-kinase, and STAT3 signaling pathways. Molecular dissection of the mechanisms involved in the interplay between these pathways identified promising new targets for therapeutic intervention. Targeting different components of the signaling cascades may provide efficient means for blocking the apparently irreversible sequence of events initiated by chronic liver inflammation and culminating in liver cancer. (C) 2013 AACR.