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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/6/1357 |
| _version_ | 1797489648693411840 |
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| author | Vincent Sauzeau Julien Beignet Christian Bailly |
| author_facet | Vincent Sauzeau Julien Beignet Christian Bailly |
| author_sort | Vincent Sauzeau |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T00:20:37Z |
| format | Article |
| id | doaj.art-2e3234be58c044c2a7a811774f2b32ab |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:20:37Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-2e3234be58c044c2a7a811774f2b32ab2023-11-23T15:43:26ZengMDPI AGBiomedicines2227-90592022-06-01106135710.3390/biomedicines10061357Rac1 as a Target to Treat Dysfunctions and Cancer of the BladderVincent Sauzeau0Julien Beignet1Christian Bailly2Université de Nantes, CHU Nantes, CNRS, INSERM, Institut du Thorax, 44202 Nantes, FranceSATT Ouest Valorisation, 30 Boulevard Vincent Gâche, CS 70211, CEDEX, 44202 Nantes, FranceOncoWitan, Scientific Consulting Office, 59290 Lille (Wasquehal), FranceBladder 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.https://www.mdpi.com/2227-9059/10/6/1357bladder cancerRho GTPasebladder dysfunctionRac inhibitorsmetastasisoveractive bladder |
| spellingShingle | Vincent Sauzeau Julien Beignet Christian Bailly Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder Biomedicines bladder cancer Rho GTPase bladder dysfunction Rac inhibitors metastasis overactive 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 | bladder cancer Rho GTPase bladder dysfunction Rac inhibitors metastasis overactive bladder |
| url | https://www.mdpi.com/2227-9059/10/6/1357 |
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