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Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Bladder pathologies, very common in the aged population, have a considerable negative impact on quality of life. Novel targets are needed to design drugs and combinations to treat diseases such as overactive bladder and bladder cancers. A promising new target is the ubiquitous Rho GTPase Rac1, frequ...

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Detalles Bibliográficos
Autores principales: Sauzeau, Vincent, Beignet, Julien, Bailly, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219850/
https://www.ncbi.nlm.nih.gov/pubmed/35740379
http://dx.doi.org/10.3390/biomedicines10061357
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author Sauzeau, Vincent
Beignet, Julien
Bailly, Christian
author_facet Sauzeau, Vincent
Beignet, Julien
Bailly, Christian
author_sort Sauzeau, Vincent
collection PubMed
description Bladder pathologies, very common in the aged population, have a considerable negative impact on quality of life. Novel targets are needed to design drugs and combinations to treat diseases such as overactive bladder and bladder cancers. A promising new target is the ubiquitous Rho GTPase Rac1, frequently dysregulated and overexpressed in bladder pathologies. We have analyzed the roles of Rac1 in different bladder pathologies, including bacterial infections, diabetes-induced bladder dysfunctions and bladder cancers. The contribution of the Rac1 protein to tumorigenesis, tumor progression, epithelial-mesenchymal transition of bladder cancer cells and their metastasis has been analyzed. Small molecules selectively targeting Rac1 have been discovered or designed, and two of them—NSC23766 and EHT 1864—have revealed activities against bladder cancer. Their mode of interaction with Rac1, at the GTP binding site or the guanine nucleotide exchange factors (GEF) interaction site, is discussed. Our analysis underlines the possibility of targeting Rac1 with small molecules with the objective to combat bladder dysfunctions and to reduce lower urinary tract symptoms. Finally, the interest of a Rac1 inhibitor to treat advanced chemoresistance prostate cancer, while reducing the risk of associated bladder dysfunction, is discussed. There is hope for a better management of bladder pathologies via Rac1-targeted approaches.
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spelling pubmed-92198502022-06-24 Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder Sauzeau, Vincent Beignet, Julien Bailly, Christian Biomedicines Review Bladder pathologies, very common in the aged population, have a considerable negative impact on quality of life. Novel targets are needed to design drugs and combinations to treat diseases such as overactive bladder and bladder cancers. A promising new target is the ubiquitous Rho GTPase Rac1, frequently dysregulated and overexpressed in bladder pathologies. We have analyzed the roles of Rac1 in different bladder pathologies, including bacterial infections, diabetes-induced bladder dysfunctions and bladder cancers. The contribution of the Rac1 protein to tumorigenesis, tumor progression, epithelial-mesenchymal transition of bladder cancer cells and their metastasis has been analyzed. Small molecules selectively targeting Rac1 have been discovered or designed, and two of them—NSC23766 and EHT 1864—have revealed activities against bladder cancer. Their mode of interaction with Rac1, at the GTP binding site or the guanine nucleotide exchange factors (GEF) interaction site, is discussed. Our analysis underlines the possibility of targeting Rac1 with small molecules with the objective to combat bladder dysfunctions and to reduce lower urinary tract symptoms. Finally, the interest of a Rac1 inhibitor to treat advanced chemoresistance prostate cancer, while reducing the risk of associated bladder dysfunction, is discussed. There is hope for a better management of bladder pathologies via Rac1-targeted approaches. MDPI 2022-06-08 /pmc/articles/PMC9219850/ /pubmed/35740379 http://dx.doi.org/10.3390/biomedicines10061357 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
Sauzeau, Vincent
Beignet, Julien
Bailly, Christian
Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder
title Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder
title_full Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder
title_fullStr Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder
title_full_unstemmed Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder
title_short Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder
title_sort rac1 as a target to treat dysfunctions and cancer of the bladder
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219850/
https://www.ncbi.nlm.nih.gov/pubmed/35740379
http://dx.doi.org/10.3390/biomedicines10061357
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