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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9496094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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