Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study

NF-kappa B pathway consists of canonical and non-canonical pathways. The canonical NF-kappa B is activated by various stimuli, transducing a quick but transient transcriptional activity, to regulate the expression of various proinflammatory genes and also serve as the critical mediator for inflammatory response. Meanwhile, the activation of the non-canonical NF-kappa B pathway occurs through a handful of TNF receptor superfamily members. Since the activation of this pathway involves protein synthesis, the kinetics of non-canonical NF-kappa B activation is slow but persistent, in concordance with its biological functions in the development of immune cell and lymphoid organ, immune homeostasis and immune response. The activation of the canonical and non-canonical NF-kappa B pathway is tightly controlled, highlighting the vital roles of ubiquitination in these pathways. Emerging studies indicate that dysregulated NF-kappa B activity causes inflammation-related diseases as well as cancers, and NF-kappa B has been long proposed as the potential target for therapy of diseases. This review attempts to summarize our current knowledge and updates on the mechanisms of NF-kappa B pathway regulation and the potential therapeutic application of inhibition of NF-kappa B signaling in cancer and inflammatory diseases.