Intersecting pathways in inflammation and cancer: Hepatocellular carcinoma as a paradigm

Viral infection and chemical carcinogens trigger somatic changes resulting in activation of oncogenes during tumor initiation in the development of cancer. However, a critical interaction resides in the synergism between these somatic changes and an inflamed tumor microenvironment where myeloid and hematopoietic cells are subverted to enhance tumor progression. The causative molecular mechanisms leading to the development of hepatocellular cancer remain incompletely understood but appear to result from multiple factors related to direct hepatocyte injury and the ensuing inflammatory changes mediated by the host response to tissue injury, DNA damage, repair of cellular damage, and chronic, repetitive injury. In this review, the molecular and cellular changes that regulate inflammation and tissue repair will be compared to the activated local tumor microenvironment. Cell-cell signaling within this microenvironment that enhances tumor progression and inhibits anti-tumor immunity will be discussed.