Role of nonresolving inflammation in hepatocellular carcinoma development and progression

The extrinsic and intrinsic pathways that trigger nonresolving inflammation during hepatocarcinogenesis. The extrinsic pathway is driven by exogenous factors (e.g., the PAMPs from pathogens or DAMPs from dead cells), which are able to trigger a persistent inflammatory response by engaging the receptors expressed in the inflammatory cells and establish an inflammatory condition that increase cancer risk. On the other hand, the intrinsic pathway is induced by alterations in cancer-associated genetic factors (e.g., mutation of either oncogenes or tumor suppressor genes), which activate the expression of inflammation-related program. Both of these pathways activate transcription factors (e.g., NF-κB, STAT3) that coordinate the production of inflammatory mediators, including cytokines, chemokines, ROS, NOS, prostaglandins and so on, generating a pro-tumoric inflammatory microenvironment in the live