Abstract Since nuclear factor of ?-light chain of enhancer-activated B cells (NF-?B) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism of NF-?B for 35 years, which lead to significant progress. Meanwhile, the molecular mechanisms regulating NF-?B activation have also been illuminated, the cascades of signaling events leading to NF-?B activity and key components of the NF-?B pathway are also identified. It has been suggested NF-?B plays an important role in human diseases, especially inflammation-related diseases. These studies make the NF-?B an attractive target for disease treatment. This review aims to summarize the knowledge of the family members of NF-?B, as well as the basic mechanisms of NF-?B signaling pathway activation. We will also review the effects of dysregulated NF-?B on inflammation, tumorigenesis, and tumor microenvironment. The progression of the translational study and drug development targeting NF-?B for inflammatory diseases and cancer treatment and the potential obstacles will be discussed. Further investigations on the precise functions of NF-?B in the physiological and pathological settings and underlying mechanisms are in the urgent need to develop drugs targeting NF-?B for inflammatory diseases and cancer treatment, with minimal side effects.
- signal transduction