Drug Repositioning of the α<sub>1</sub>-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?
Failure of conventional treatments is often observed in cancer management and this requires the development of alternative therapeutic strategies. However, new drug development is known to be a high-failure process because of the possibility of a lower efficacy than expected for the drug or appearan...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/15/5339 |
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| author | Romane Florent Laurent Poulain Monique N'Diaye |
| author_facet | Romane Florent Laurent Poulain Monique N'Diaye |
| author_sort | Romane Florent |
| collection | DOAJ |
| description | Failure of conventional treatments is often observed in cancer management and this requires the development of alternative therapeutic strategies. However, new drug development is known to be a high-failure process because of the possibility of a lower efficacy than expected for the drug or appearance of non-manageable side effects. Another way to find alternative therapeutic drugs consists in identifying new applications for drugs already approved for a particular disease: a concept named “drug repurposing”. In this context, several studies demonstrated the potential anti-tumour activity exerted by α1-adrenergic receptor antagonists and notably renewed interest for naftopidil as an anti-cancer drug. Naftopidil is used for benign prostatic hyperplasia management in Japan and a retrospective study brought out a reduced incidence of prostate cancer in patients that had been prescribed this drug. Further studies showed that naftopidil exerted anti-proliferative and cytotoxic effects on prostate cancer as well as several other cancer types in vitro, as well as ex vivo and in vivo. Moreover, naftopidil was demonstrated to modulate the expression of Bcl-2 family pro-apoptotic members which could be used to sensitise cancer cells to targeting therapies and to overcome resistance of cancer cells to apoptosis. For most of these anti-cancer effects, the molecular pathway is either not fully deciphered or shown to involve α1-adrenergic receptor-independent pathway, suggesting off target transduction signals. In order to improve its efficacy, naftopidil analogues were designed and shown to be effective in several studies. Thereby, naftopidil appears to display anti-cancer properties on different cancer types and could be considered as a candidate for drug repurposing although its anti-cancerous activities need to be studied more deeply in prospective randomized clinical trials. |
| first_indexed | 2024-03-10T18:10:33Z |
| format | Article |
| id | doaj.art-e30fbfc2201b47f6b50810828fecece4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:10:33Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e30fbfc2201b47f6b50810828fecece42023-11-20T08:08:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012115533910.3390/ijms21155339Drug Repositioning of the α<sub>1</sub>-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?Romane Florent0Laurent Poulain1Monique N'Diaye2Normandie Univ, UNICAEN, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA axis (Biology and Innovative Therapeutics for Ovarian Cancers), 14000 Caen, FranceNormandie Univ, UNICAEN, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA axis (Biology and Innovative Therapeutics for Ovarian Cancers), 14000 Caen, FranceNormandie Univ, UNICAEN, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA axis (Biology and Innovative Therapeutics for Ovarian Cancers), 14000 Caen, FranceFailure of conventional treatments is often observed in cancer management and this requires the development of alternative therapeutic strategies. However, new drug development is known to be a high-failure process because of the possibility of a lower efficacy than expected for the drug or appearance of non-manageable side effects. Another way to find alternative therapeutic drugs consists in identifying new applications for drugs already approved for a particular disease: a concept named “drug repurposing”. In this context, several studies demonstrated the potential anti-tumour activity exerted by α1-adrenergic receptor antagonists and notably renewed interest for naftopidil as an anti-cancer drug. Naftopidil is used for benign prostatic hyperplasia management in Japan and a retrospective study brought out a reduced incidence of prostate cancer in patients that had been prescribed this drug. Further studies showed that naftopidil exerted anti-proliferative and cytotoxic effects on prostate cancer as well as several other cancer types in vitro, as well as ex vivo and in vivo. Moreover, naftopidil was demonstrated to modulate the expression of Bcl-2 family pro-apoptotic members which could be used to sensitise cancer cells to targeting therapies and to overcome resistance of cancer cells to apoptosis. For most of these anti-cancer effects, the molecular pathway is either not fully deciphered or shown to involve α1-adrenergic receptor-independent pathway, suggesting off target transduction signals. In order to improve its efficacy, naftopidil analogues were designed and shown to be effective in several studies. Thereby, naftopidil appears to display anti-cancer properties on different cancer types and could be considered as a candidate for drug repurposing although its anti-cancerous activities need to be studied more deeply in prospective randomized clinical trials.https://www.mdpi.com/1422-0067/21/15/5339cancerdrug repurposingα<sub>1</sub>-adrenergic receptor antagonistsnaftopidil |
| spellingShingle | Romane Florent Laurent Poulain Monique N'Diaye Drug Repositioning of the α<sub>1</sub>-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug? International Journal of Molecular Sciences cancer drug repurposing α<sub>1</sub>-adrenergic receptor antagonists naftopidil |
| title | Drug Repositioning of the α<sub>1</sub>-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug? |
| title_full | Drug Repositioning of the α<sub>1</sub>-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug? |
| title_fullStr | Drug Repositioning of the α<sub>1</sub>-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug? |
| title_full_unstemmed | Drug Repositioning of the α<sub>1</sub>-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug? |
| title_short | Drug Repositioning of the α<sub>1</sub>-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug? |
| title_sort | drug repositioning of the α sub 1 sub adrenergic receptor antagonist naftopidil a potential new anti cancer drug |
| topic | cancer drug repurposing α<sub>1</sub>-adrenergic receptor antagonists naftopidil |
| url | https://www.mdpi.com/1422-0067/21/15/5339 |
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