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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/9/2233 |
| _version_ | 1797490877210296320 |
|---|---|
| author | Daniela Verzella Jessica Cornice Paola Arboretto Davide Vecchiotti Mauro Di Vito Nolfi Daria Capece Francesca Zazzeroni Guido Franzoso |
| author_facet | Daniela Verzella Jessica Cornice Paola Arboretto Davide Vecchiotti Mauro Di Vito Nolfi Daria Capece Francesca Zazzeroni Guido Franzoso |
| author_sort | Daniela Verzella |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T00:39:21Z |
| format | Article |
| id | doaj.art-7e5eaff61d704563be5a56672d26381b |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:39:21Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-7e5eaff61d704563be5a56672d26381b2023-11-23T15:11:24ZengMDPI AGBiomedicines2227-90592022-09-01109223310.3390/biomedicines10092233The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable TargetDaniela Verzella0Jessica Cornice1Paola Arboretto2Davide Vecchiotti3Mauro Di Vito Nolfi4Daria Capece5Francesca Zazzeroni6Guido Franzoso7Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Immunology and Inflammation, Imperial College London, London W12 0NN, UKDepartment of Immunology and Inflammation, Imperial College London, London W12 0NN, UKDepartment of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Biotechnological and Applied Clinical Sciences (DISCAB), University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Immunology and Inflammation, Imperial College London, London W12 0NN, UKNF-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.https://www.mdpi.com/2227-9059/10/9/2233nuclear factor κBNF-κB inhibitorscancer therapytargeted therapy |
| spellingShingle | Daniela Verzella Jessica Cornice Paola Arboretto Davide Vecchiotti Mauro Di Vito Nolfi Daria Capece Francesca Zazzeroni Guido Franzoso The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target Biomedicines nuclear factor κB NF-κB inhibitors cancer therapy targeted therapy |
| 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 | nuclear factor κB NF-κB inhibitors cancer therapy targeted therapy |
| url | https://www.mdpi.com/2227-9059/10/9/2233 |
| work_keys_str_mv | AT danielaverzella thenfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT jessicacornice thenfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT paolaarboretto thenfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT davidevecchiotti thenfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT maurodivitonolfi thenfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT dariacapece thenfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT francescazazzeroni thenfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT guidofranzoso thenfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT danielaverzella nfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT jessicacornice nfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT paolaarboretto nfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT davidevecchiotti nfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT maurodivitonolfi nfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT dariacapece nfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT francescazazzeroni nfkbpharmacopeianovelstrategiestosubdueanintractabletarget AT guidofranzoso nfkbpharmacopeianovelstrategiestosubdueanintractabletarget |