Evaluation of Darolutamide (ODM201) Efficiency on Androgen Receptor Mutants Reported to Date in Prostate Cancer Patients
Resistance to drug treatments is common in prostate cancer (PCa), and the gain-of-function mutations in human androgen receptor (AR) represent one of the most dominant drivers of progression to resistance to AR pathway inhibitors (ARPI). Previously, we evaluated the in vitro response of 24 AR mutati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/2939 |
| _version_ | 1797530489516457984 |
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| author | Nada Lallous Oliver Snow Christophe Sanchez Ana Karla Parra Nuñez Bei Sun Ahmed Hussain Joseph Lee Helene Morin Eric Leblanc Martin E. Gleave Artem Cherkasov |
| author_facet | Nada Lallous Oliver Snow Christophe Sanchez Ana Karla Parra Nuñez Bei Sun Ahmed Hussain Joseph Lee Helene Morin Eric Leblanc Martin E. Gleave Artem Cherkasov |
| author_sort | Nada Lallous |
| collection | DOAJ |
| description | Resistance to drug treatments is common in prostate cancer (PCa), and the gain-of-function mutations in human androgen receptor (AR) represent one of the most dominant drivers of progression to resistance to AR pathway inhibitors (ARPI). Previously, we evaluated the in vitro response of 24 AR mutations, identified in men with castration-resistant PCa, to five AR antagonists. In the current work, we evaluated 44 additional PCa-associated AR mutants, reported in the literature, and thus expanded the study of the effect of darolutamide to a total of 68 AR mutants. Unlike other AR antagonists, we demonstrate that darolutamide exhibits consistent efficiency against all characterized gain-of-function mutations in a full-length AR. Additionally, the response of the AR mutants to clinically used bicalutamide and enzalutamide, as well as to major endogenous steroids (DHT, estradiol, progesterone and hydrocortisone), was also investigated. As genomic profiling of PCa patients becomes increasingly feasible, the developed “AR functional encyclopedia” could provide decision-makers with a tool to guide the treatment choice for PCa patients based on their AR mutation status. |
| first_indexed | 2024-03-10T10:29:43Z |
| format | Article |
| id | doaj.art-dc7df70414a64cac99cb3d72f46f924c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:29:43Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dc7df70414a64cac99cb3d72f46f924c2023-11-21T23:47:28ZengMDPI AGCancers2072-66942021-06-011312293910.3390/cancers13122939Evaluation of Darolutamide (ODM201) Efficiency on Androgen Receptor Mutants Reported to Date in Prostate Cancer PatientsNada Lallous0Oliver Snow1Christophe Sanchez2Ana Karla Parra Nuñez3Bei Sun4Ahmed Hussain5Joseph Lee6Helene Morin7Eric Leblanc8Martin E. Gleave9Artem Cherkasov10Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak St., Vancouver, BC V6H 3Z6, CanadaResistance to drug treatments is common in prostate cancer (PCa), and the gain-of-function mutations in human androgen receptor (AR) represent one of the most dominant drivers of progression to resistance to AR pathway inhibitors (ARPI). Previously, we evaluated the in vitro response of 24 AR mutations, identified in men with castration-resistant PCa, to five AR antagonists. In the current work, we evaluated 44 additional PCa-associated AR mutants, reported in the literature, and thus expanded the study of the effect of darolutamide to a total of 68 AR mutants. Unlike other AR antagonists, we demonstrate that darolutamide exhibits consistent efficiency against all characterized gain-of-function mutations in a full-length AR. Additionally, the response of the AR mutants to clinically used bicalutamide and enzalutamide, as well as to major endogenous steroids (DHT, estradiol, progesterone and hydrocortisone), was also investigated. As genomic profiling of PCa patients becomes increasingly feasible, the developed “AR functional encyclopedia” could provide decision-makers with a tool to guide the treatment choice for PCa patients based on their AR mutation status.https://www.mdpi.com/2072-6694/13/12/2939androgen receptorantagonistscastration-resistant prostate cancer (CRPC)darolutamidedrug resistancemutations |
| spellingShingle | Nada Lallous Oliver Snow Christophe Sanchez Ana Karla Parra Nuñez Bei Sun Ahmed Hussain Joseph Lee Helene Morin Eric Leblanc Martin E. Gleave Artem Cherkasov Evaluation of Darolutamide (ODM201) Efficiency on Androgen Receptor Mutants Reported to Date in Prostate Cancer Patients Cancers androgen receptor antagonists castration-resistant prostate cancer (CRPC) darolutamide drug resistance mutations |
| title | Evaluation of Darolutamide (ODM201) Efficiency on Androgen Receptor Mutants Reported to Date in Prostate Cancer Patients |
| title_full | Evaluation of Darolutamide (ODM201) Efficiency on Androgen Receptor Mutants Reported to Date in Prostate Cancer Patients |
| title_fullStr | Evaluation of Darolutamide (ODM201) Efficiency on Androgen Receptor Mutants Reported to Date in Prostate Cancer Patients |
| title_full_unstemmed | Evaluation of Darolutamide (ODM201) Efficiency on Androgen Receptor Mutants Reported to Date in Prostate Cancer Patients |
| title_short | Evaluation of Darolutamide (ODM201) Efficiency on Androgen Receptor Mutants Reported to Date in Prostate Cancer Patients |
| title_sort | evaluation of darolutamide odm201 efficiency on androgen receptor mutants reported to date in prostate cancer patients |
| topic | androgen receptor antagonists castration-resistant prostate cancer (CRPC) darolutamide drug resistance mutations |
| url | https://www.mdpi.com/2072-6694/13/12/2939 |
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