NF-κB in the crosshairs: Rethinking an old riddle. (February 2018)

• Record Type: Journal Article
• Authors: Bennett, Jason; Capece, Daria; Begalli, Federica; Verzella, Daniela; D'Andrea, Daniel; Tornatore, Laura; Franzoso, Guido
• Is Part Of: International journal of biochemistry & cell biology. Volume 95(2018)
• Page Start: 108
• Page End: 112
• Publication Date: 2018-02
• Subjects: BCL-2 B-cell lymphoma 2 -- BCL-XL B-cell lymphoma-extra large -- BFL-1 Bcl-2-related gene expressed in foetal liver -- cIAP cellular inhibitor of apoptosis -- cFLIP cellular FLICE-inhibitory protein -- CLL chronic lymphocytic leukaemia -- DIABLO direct inhibitor of apoptosis protein (IAP)-binding protein with low pI -- DLBCL diffuse large B-cell lymphoma -- FDA US Food and Drug Administration -- FLICE FADD-like IL-1β-converting enzyme -- GADD45β growth arrest and DNA damage inducible β -- GBM glioblastoma multiforme -- IKK IκBα kinase -- IL-1β interleukin-1β -- IκBα nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor α -- JNK c-Jun N-terminal kinase -- MALT mucosa-associated lymphoid tissue -- MAP mitogen activated protein -- MCL1 myeloid cell leukaemia sequence 1 -- NF-κB nuclear factor κ B (nuclear factor binding to the κ-light-chain-enhancer B site) -- PTEN phosphatase and tensin homolog -- RAS rat sarcoma virus oncogene -- SCF SKP1-Cullin 1-F-box protein -- SMAC second mitochondria-derived activator of caspases -- TME tumour microenvironment -- βTrCPP β-transducin repeat-containing proteint -- XIAP X chromosome-linked inhibitor of apoptosis protein; Cancer -- NF-κB -- B -- IKKβ -- GADD45β -- DTP3; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2017.12.020
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: NF-κB transcription factors are central coordinating regulators of immunity, inflammation and cell survival. NF-κB pathway is aberrantly and stably activated in cancer. The ubiquitous presence and pleiotropic physiological role of NF-κB dimers have thus far prevented the development of any clinically useful NF-κB inhibitor. Emerging therapeutic approaches aim to achieve the cancer-selective inhibition of the NF-κB pathway as a way to overcome the preclusive toxicities of conventional IKKβ/NF-κB-targeting drugs. Abstract: Constitutive NF-κB signalling has been implicated in the pathogenesis of most human malignancies and virtually all non-malignant pathologies. Accordingly, the NF-κB pathway has been aggressively pursued as an attractive therapeutic target for drug discovery. However, the severe on-target toxicities associated with systemic NF-κB inhibition have thus far precluded the development of a clinically useful, NF-κB-targeting medicine as a way to treat patients with either oncological or non-oncological diseases. This minireview discusses some of the more promising approaches currently being developed to circumvent the preclusive safety liabilities of global NF-κB blockade by selectively targeting pathogenic NF-κB signalling in cancer, while preserving the multiple physiological functions of NF-κB in host defence responses and tissue homeostasis.