title: NF-κB and the link between inflammation and cancer.
abstract: The nuclear factor-κB (NF-κB) 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-κB/RelA and identification of its kinship to the v-Rel oncogene, it was anticipated that NF-κB itself would be involved in cancer development. Oncogenic activating mutations in NF-κB genes are rare and have been identified only in some lymphoid malignancies, while most NF-κB activating mutations in lymphoid malignancies occur in upstream signaling components that feed into NF-κB. NF-κB activation is also prevalent in carcinomas, in which NF-κB activation is mainly driven by inflammatory cytokines within the tumor microenvironment. Importantly, however, in all malignancies, NF-κB 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-κB have made its therapeutic targeting a challenge.
authors.affiliation: Cleveland Clinic Foundation, Department of Cell Biology, Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: DiDonato
authors.forename: Frank
authors.initials: F
authors.lastname: Mercurio
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D015513:Oncogene Proteins; D047428:Protein Kinase Inhibitors; D025521:Tumor Suppressor Proteins