It has been established that cancer can be promoted and exacerbated by inflammation. Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, and its long-term prognosis remains poor. Although HCC is a complex and heterogeneous tumor with several genomic mutations, it usually develops in the context of chronic liver damage and inflammation, suggesting that understanding the mechanism(s) of inflammation-mediated hepatocarcinogenesis is essential for the treatment and prevention of HCC. Chronic liver damage induces a persistent cycle of necro-inflammation and hepatocyte regeneration, resulting in genetic mutations in hepatocytes and expansion of initiated cells, eventually leading to HCC development. Recently, several inflammation- and stress-related signaling pathways have been identified as key players in these processes, which include the nuclear factor-κB, signal transducer and activator of transcription, and stress-activated mitogen- activated protein kinase pathways. Although these pathways may suggest potential therapeutic targets, they have a wide range of functions and complex crosstalk occurs among them. This review focuses on recent advances in our understanding of the roles of these signaling pathways in hepatocarcinogenesis.
Keywords: Apoptosis signal-regulating kinase 1; Hepatocellular carcinoma; Inflammation; Mitogen-activated protein kinase; Nuclear factor-κB; Signal transducer and activator of transcription; Transforming growth factor-activated kinase 1; c-Jun NH2-terminal kinase; p38.