A phosphorylation switch controls androgen biosynthesis in prostate cancer
Androgen biosynthesis enzyme 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 has emerged as a potential driver for therapeutic resistance in prostate cancer. Patients with homozygous HSD3B1(1245C) inheritance are intrinsically more resistant to currently available androgen/androgen...
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2023-01-01
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| Series: | The Journal of Clinical Investigation |
| Online Access: | https://doi.org/10.1172/JCI166499 |
| _version_ | 1797634498617147392 |
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| author | Yun Qiu |
| author_facet | Yun Qiu |
| author_sort | Yun Qiu |
| collection | DOAJ |
| description | Androgen biosynthesis enzyme 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 has emerged as a potential driver for therapeutic resistance in prostate cancer. Patients with homozygous HSD3B1(1245C) inheritance are intrinsically more resistant to currently available androgen/androgen receptor–targeting (AR-targeting) drugs. In this issue of the JCI, Li et al. present data on the regulation of 3βHSD1 phosphorylation and activity by tyrosine kinase BMX. Inhibition of BMX activity by genetic or pharmacologic approaches blocked androgen biosynthesis in prostate cancer cells and inhibited tumor growth in preclinical xenograft models. The findings provide insights into mechanisms underlying castration resistance in prostate cancer and reveal a potential strategy to circumvent therapeutic resistance in patients with homozygous HSD3B1(1245C) inheritance. |
| first_indexed | 2024-03-11T12:08:42Z |
| format | Article |
| id | doaj.art-4deb8d42bedc484f8b4a82362439b2b8 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:08:42Z |
| publishDate | 2023-01-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-4deb8d42bedc484f8b4a82362439b2b82023-11-07T16:19:47ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-01-011332A phosphorylation switch controls androgen biosynthesis in prostate cancerYun QiuAndrogen biosynthesis enzyme 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 has emerged as a potential driver for therapeutic resistance in prostate cancer. Patients with homozygous HSD3B1(1245C) inheritance are intrinsically more resistant to currently available androgen/androgen receptor–targeting (AR-targeting) drugs. In this issue of the JCI, Li et al. present data on the regulation of 3βHSD1 phosphorylation and activity by tyrosine kinase BMX. Inhibition of BMX activity by genetic or pharmacologic approaches blocked androgen biosynthesis in prostate cancer cells and inhibited tumor growth in preclinical xenograft models. The findings provide insights into mechanisms underlying castration resistance in prostate cancer and reveal a potential strategy to circumvent therapeutic resistance in patients with homozygous HSD3B1(1245C) inheritance.https://doi.org/10.1172/JCI166499 |
| spellingShingle | Yun Qiu A phosphorylation switch controls androgen biosynthesis in prostate cancer The Journal of Clinical Investigation |
| title | A phosphorylation switch controls androgen biosynthesis in prostate cancer |
| title_full | A phosphorylation switch controls androgen biosynthesis in prostate cancer |
| title_fullStr | A phosphorylation switch controls androgen biosynthesis in prostate cancer |
| title_full_unstemmed | A phosphorylation switch controls androgen biosynthesis in prostate cancer |
| title_short | A phosphorylation switch controls androgen biosynthesis in prostate cancer |
| title_sort | phosphorylation switch controls androgen biosynthesis in prostate cancer |
| url | https://doi.org/10.1172/JCI166499 |
| work_keys_str_mv | AT yunqiu aphosphorylationswitchcontrolsandrogenbiosynthesisinprostatecancer AT yunqiu phosphorylationswitchcontrolsandrogenbiosynthesisinprostatecancer |