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The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target

NF-κB transcription factors are major drivers of tumor initiation and progression. NF-κB signaling is constitutively activated by genetic alterations or environmental signals in many human cancers, where it contributes to almost all hallmarks of malignancy, including sustained proliferation, cell de...

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Autores principales: Verzella, Daniela, Cornice, Jessica, Arboretto, Paola, Vecchiotti, Davide, Di Vito Nolfi, Mauro, Capece, Daria, Zazzeroni, Francesca, Franzoso, Guido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496094/
https://www.ncbi.nlm.nih.gov/pubmed/36140335
http://dx.doi.org/10.3390/biomedicines10092233
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author Verzella, Daniela
Cornice, Jessica
Arboretto, Paola
Vecchiotti, Davide
Di Vito Nolfi, Mauro
Capece, Daria
Zazzeroni, Francesca
Franzoso, Guido
author_facet Verzella, Daniela
Cornice, Jessica
Arboretto, Paola
Vecchiotti, Davide
Di Vito Nolfi, Mauro
Capece, Daria
Zazzeroni, Francesca
Franzoso, Guido
author_sort Verzella, Daniela
collection PubMed
description NF-κB transcription factors are major drivers of tumor initiation and progression. NF-κB signaling is constitutively activated by genetic alterations or environmental signals in many human cancers, where it contributes to almost all hallmarks of malignancy, including sustained proliferation, cell death resistance, tumor-promoting inflammation, metabolic reprogramming, tissue invasion, angiogenesis, and metastasis. As such, the NF-κB pathway is an attractive therapeutic target in a broad range of human cancers, as well as in numerous non-malignant diseases. Currently, however, there is no clinically useful NF-κB inhibitor to treat oncological patients, owing to the preclusive, on-target toxicities of systemic NF-κB blockade. In this review, we discuss the principal and most promising strategies being developed to circumvent the inherent limitations of conventional IκB kinase (IKK)/NF-κB-targeting drugs, focusing on new molecules that target upstream regulators or downstream effectors of oncogenic NF-κB signaling, as well as agents targeting individual NF-κB subunits.
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spelling pubmed-94960942022-09-23 The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target Verzella, Daniela Cornice, Jessica Arboretto, Paola Vecchiotti, Davide Di Vito Nolfi, Mauro Capece, Daria Zazzeroni, Francesca Franzoso, Guido Biomedicines Review NF-κB transcription factors are major drivers of tumor initiation and progression. NF-κB signaling is constitutively activated by genetic alterations or environmental signals in many human cancers, where it contributes to almost all hallmarks of malignancy, including sustained proliferation, cell death resistance, tumor-promoting inflammation, metabolic reprogramming, tissue invasion, angiogenesis, and metastasis. As such, the NF-κB pathway is an attractive therapeutic target in a broad range of human cancers, as well as in numerous non-malignant diseases. Currently, however, there is no clinically useful NF-κB inhibitor to treat oncological patients, owing to the preclusive, on-target toxicities of systemic NF-κB blockade. In this review, we discuss the principal and most promising strategies being developed to circumvent the inherent limitations of conventional IκB kinase (IKK)/NF-κB-targeting drugs, focusing on new molecules that target upstream regulators or downstream effectors of oncogenic NF-κB signaling, as well as agents targeting individual NF-κB subunits. MDPI 2022-09-08 /pmc/articles/PMC9496094/ /pubmed/36140335 http://dx.doi.org/10.3390/biomedicines10092233 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Verzella, Daniela
Cornice, Jessica
Arboretto, Paola
Vecchiotti, Davide
Di Vito Nolfi, Mauro
Capece, Daria
Zazzeroni, Francesca
Franzoso, Guido
The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target
title The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target
title_full The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target
title_fullStr The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target
title_full_unstemmed The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target
title_short The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target
title_sort nf-κb pharmacopeia: novel strategies to subdue an intractable target
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496094/
https://www.ncbi.nlm.nih.gov/pubmed/36140335
http://dx.doi.org/10.3390/biomedicines10092233
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