Zhang Tao, Ma Chao, Zhang Zhiqiang, Zhang Huiyuan, Hu Hongbo
Cancer Center and Center for Immunology and Hematology West China Hospital Sichuan University Chengdu Sichuan China.
Immunobiology and Transplant Science Center Houston Methodist Hospital Houston Texas USA.
MedComm (2020). 2021 Dec 16;2(4):618-653. doi: 10.1002/mco2.104. eCollection 2021 Dec.
Since nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism of NF-κB for 35 years, which lead to significant progress. Meanwhile, the molecular mechanisms regulating NF-κB activation have also been illuminated, the cascades of signaling events leading to NF-κB activity and key components of the NF-κB pathway are also identified. It has been suggested NF-κB plays an important role in human diseases, especially inflammation-related diseases. These studies make the NF-κB an attractive target for disease treatment. This review aims to summarize the knowledge of the family members of NF-κB, as well as the basic mechanisms of NF-κB signaling pathway activation. We will also review the effects of dysregulated NF-κB on inflammation, tumorigenesis, and tumor microenvironment. The progression of the translational study and drug development targeting NF-κB for inflammatory diseases and cancer treatment and the potential obstacles will be discussed. Further investigations on the precise functions of NF-κB in the physiological and pathological settings and underlying mechanisms are in the urgent need to develop drugs targeting NF-κB for inflammatory diseases and cancer treatment, with minimal side effects.
自1986年发现增强子激活的B细胞κ轻链核因子(NF-κB)以来,35年间人们为了解NF-κB的功能及其调控机制付出了巨大努力,并取得了显著进展。同时,调控NF-κB激活的分子机制也已阐明,导致NF-κB活性的信号事件级联以及NF-κB信号通路的关键组分也已确定。有研究表明,NF-κB在人类疾病尤其是炎症相关疾病中起重要作用。这些研究使NF-κB成为疾病治疗的一个有吸引力的靶点。本综述旨在总结NF-κB家族成员的相关知识,以及NF-κB信号通路激活的基本机制。我们还将综述NF-κB失调对炎症、肿瘤发生和肿瘤微环境的影响。将讨论针对NF-κB用于炎症性疾病和癌症治疗的转化研究进展和药物开发情况以及潜在障碍。迫切需要进一步研究NF-κB在生理和病理环境中的精确功能及其潜在机制,以开发针对炎症性疾病和癌症治疗且副作用最小的靶向NF-κB的药物。