title: p53 and the Carcinogenicity of Chronic Inflammation.
abstract: Chronic inflammation is a major cancer predisposition factor. Constitutive activation of the inflammation-driving NF-κB pathway commonly observed in cancer or developed in normal tissues because of persistent infections or endogenous tissue irritating factors, including products of secretion by senescent cells accumulating with age, markedly represses p53 functions. In its turn, p53 acts as a suppressor of inflammation helping to keep it within safe limits. The antagonistic relationship between p53 and NF-κB is controlled by multiple mechanisms and reflects cardinal differences in organismal responses to intrinsic and extrinsic cell stresses driven by these two transcription factors, respectively. This provides an opportunity for developing drugs to treat diseases associated with inappropriate activity of either p53 or NF-κB through targeting the opposing pathway. Several drug candidates of this kind are currently in clinical testing. These include anticancer small molecules capable of simultaneous suppression of p53 and activation of NF-κB and NF-κB-activating biologics that counteract p53-mediated pathologies associated with systemic genotoxic stresses such as acute radiation syndrome and side effects of cancer treatment.
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Gudkov
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Komarova
mesh_terms: D016922:Cellular Senescence; D004249:DNA Damage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53