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The NF-κB pharmacopeia: novel strategies to subdue an intractable target
File(s)
biomedicines-10-02233-v2.pdf (2.21 MB)
Published version
Author(s)
Verzella, Daniela
Cornice, Jessica
Arboretto, Paola
Vecchiotti, Davide
Di Vito Nolfi, Mauro
Type
Journal Article
Abstract
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.
Date Issued
2022-09-08
Date Acceptance
2022-09-08
Citation
Biomedicine, 2022, 10 (9)
URI
DOI
ISSN
0970-2067
Publisher
Indian Assoc of Biomedical Scientists
Journal / Book Title
Biomedicine
Volume
10
Issue
9
Copyright Statement
© 2022 by the authors.
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/).
License URL
Sponsor
Medical Research Council (MRC)
Cancer Research UK
Bloodwise
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Grant Number
MR/L005069/1
15115
15003
RDF01
MR/V027581/1
Publication Status
Published
Article Number
ARTN 2233
Date Publish Online
2022-09-08