Is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy?
Androgen deprivation therapy (ADT) is the longstanding treatment for advanced prostate cancer (PC) because androgen receptor (AR) is the key therapeutic vulnerability for this disease. Bipolar androgen therapy (BAT) — the rapid cycling of supraphysiologic androgen (SPA) and low serum testosterone le...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2022-12-01
|
| Series: | The Journal of Clinical Investigation |
| Online Access: | https://doi.org/10.1172/JCI165357 |
| _version_ | 1797634486436888576 |
|---|---|
| author | Nahuel Peinetti Marijo Bilusic Kerry L. Burnstein |
| author_facet | Nahuel Peinetti Marijo Bilusic Kerry L. Burnstein |
| author_sort | Nahuel Peinetti |
| collection | DOAJ |
| description | Androgen deprivation therapy (ADT) is the longstanding treatment for advanced prostate cancer (PC) because androgen receptor (AR) is the key therapeutic vulnerability for this disease. Bipolar androgen therapy (BAT) — the rapid cycling of supraphysiologic androgen (SPA) and low serum testosterone levels — is an alternative concept, but not all patients respond and acquired resistance can occur. In this issue of the JCI, Sena et al. developed a gene signature indicative of high AR activity to predict patient response to BAT, including a decline in both serum prostate-specific antigen (PSA) and tumor volume. Preclinical models showed that AR-mediated suppression of MYC, known to drive PC, was associated with decreased cell growth following SPA treatment. Because BAT eventually leads to resistance, the authors tested cycling between SPA and AR antagonism in a patient-derived xenograft and observed a delay in tumor growth. These findings represent a major step toward the informed use of BAT for advanced PC. |
| first_indexed | 2024-03-11T12:09:28Z |
| format | Article |
| id | doaj.art-1d2cf0797d8e49138a0f6bb053dd79c6 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:09:28Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-1d2cf0797d8e49138a0f6bb053dd79c62023-11-07T16:19:33ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-12-0113223Is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy?Nahuel PeinettiMarijo BilusicKerry L. BurnsteinAndrogen deprivation therapy (ADT) is the longstanding treatment for advanced prostate cancer (PC) because androgen receptor (AR) is the key therapeutic vulnerability for this disease. Bipolar androgen therapy (BAT) — the rapid cycling of supraphysiologic androgen (SPA) and low serum testosterone levels — is an alternative concept, but not all patients respond and acquired resistance can occur. In this issue of the JCI, Sena et al. developed a gene signature indicative of high AR activity to predict patient response to BAT, including a decline in both serum prostate-specific antigen (PSA) and tumor volume. Preclinical models showed that AR-mediated suppression of MYC, known to drive PC, was associated with decreased cell growth following SPA treatment. Because BAT eventually leads to resistance, the authors tested cycling between SPA and AR antagonism in a patient-derived xenograft and observed a delay in tumor growth. These findings represent a major step toward the informed use of BAT for advanced PC.https://doi.org/10.1172/JCI165357 |
| spellingShingle | Nahuel Peinetti Marijo Bilusic Kerry L. Burnstein Is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy? The Journal of Clinical Investigation |
| title | Is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy? |
| title_full | Is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy? |
| title_fullStr | Is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy? |
| title_full_unstemmed | Is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy? |
| title_short | Is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy? |
| title_sort | is androgen receptor activity in metastatic prostate cancer a good biomarker for bipolar androgen therapy |
| url | https://doi.org/10.1172/JCI165357 |
| work_keys_str_mv | AT nahuelpeinetti isandrogenreceptoractivityinmetastaticprostatecanceragoodbiomarkerforbipolarandrogentherapy AT marijobilusic isandrogenreceptoractivityinmetastaticprostatecanceragoodbiomarkerforbipolarandrogentherapy AT kerrylburnstein isandrogenreceptoractivityinmetastaticprostatecanceragoodbiomarkerforbipolarandrogentherapy |