NF-κB, Inflammation, Immunity and Cancer: Coming of Age

Key Points Inflammation has been recognized as a hallmark of cancer and is known to play an essential role in the development and progression of most cancers, even those without obvious signs of inflammation and infection. Nuclear factor-κB (NF-κB), a transcription factor that is essential for inflammatory responses, is one of the most important molecules linking chronic inflammation to cancer, and its activity is tightly regulated by several mechanisms. Activation of NF-κB is primarily initiated by bacterial endotoxins such as lipopolysaccharide and pro-inflammatory cytokines such as tumour necrosis factor and IL-1. NF-κB activation occurs in cancer cells and in the tumour microenvironments of most solid cancers and haematopoietic malignancies. NF-κB activation induces various target genes, such as pro-proliferative and anti-apoptotic genes, and NF-κB signalling crosstalk affects many signalling pathways, including those involving STAT3, AP1, interferon regulatory factors, NRF2, Notch, WNT–β-catenin and p53. All known hallmarks of cancer involve NF-κB activation. In addition to enhancing cancer cell proliferation and survival, NF-κB and inflammation promote genetic and epigenetic alterations, cellular metabolic changes, the acquisition of cancer stem cell properties, epithelial-to-mesenchymal transition, invasion, angiogenesis, metastasis, therapy resistance and the suppression of antitumour immunity. The prevalence of NF-κB activation in cancer-related inflammation makes it an attractive therapeutic target with the potential for minimal side effects.