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NF-κB in the crosshairs: Rethinking an old riddle

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...

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Detalles Bibliográficos
Autores principales: Bennett, Jason, Capece, Daria, Begalli, Federica, Verzella, Daniela, D’Andrea, Daniel, Tornatore, Laura, Franzoso, Guido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562234/
https://www.ncbi.nlm.nih.gov/pubmed/29277662
http://dx.doi.org/10.1016/j.biocel.2017.12.020
Descripción
Sumario: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.