Molecular Targets in Hepatocarcinogenesis and Implications for Therapy

Hepatocarcinogenesis comprises of multiple, complex steps that occur after liver injury and usually involve several pathways, including telomere dysfunction, cell cycle, WNT/β-catenin signaling, oxidative stress and mitochondria dysfunction, autophagy, apoptosis, and AKT/mTOR signaling. Following liver injury, gene mutations, accumulation of oxidative stress, and local inflammation lead to cell proliferation, differentiation, apoptosis, and necrosis. The persistence of this vicious cycle in turn leads to further gene mutation and dysregulation of pro- and anti-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-10, IL-12, IL-13, IL-18, and transforming growth factor (TGF)-β, resulting in immune escape by means of the NF-κB and inflammasome signaling pathways. In this review, we summarize studies focusing on the roles of hepatocarcinogenesis and the immune system in liver cancer. In addition, we furnish an overview of recent basic and clinical studies to provide a strong foundation to develop novel anti-carcinogenesis targets for further treatment interventions.