NF-κB and the link between inflammation and cancer

The nuclear factor-?B (NF-?B) transcription factor family has been considered the central mediator of the inflammatory process and a key participant in innate and adaptive immune responses. Coincident with the molecular cloning of NF-?B/RelA and identification of its kinship to the v-Rel oncogene, it was anticipated that NF-?B itself would be involved in cancer development. Oncogenic activating mutations in NF-?B genes are rare and have been identified only in some lymphoid malignancies, while most NF-?B activating mutations in lymphoid malignancies occur in upstream signaling components that feed into NF-?B. NF-?B activation is also prevalent in carcinomas, in which NF-?B activation is mainly driven by inflammatory cytokines within the tumor microenvironment. Importantly, however, in all malignancies, NF-?B acts in a cell type-specific manner: activating survival genes within cancer cells and inflammation-promoting genes in components of the tumor microenvironment. Yet, the complex biological functions of NF-?B have made its therapeutic targeting a challenge.