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Intracrine androgen biosynthesis and drug resistance
Castration-resistant prostate cancer is the lethal form of prostate cancer and most commonly remains dependent on androgen receptor (AR) signaling. Current therapies use AR signaling inhibitors (ARSI) exemplified by abiraterone acetate, a P450c17 inhibitor, and enzalutamide, a potent AR antagonist....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
OAE Publishing Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992556/ https://www.ncbi.nlm.nih.gov/pubmed/35582223 http://dx.doi.org/10.20517/cdr.2020.60 |
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author | Penning, Trevor M. Asangani, Irfan A. Sprenger, Cynthia Plymate, Stephen |
author_facet | Penning, Trevor M. Asangani, Irfan A. Sprenger, Cynthia Plymate, Stephen |
author_sort | Penning, Trevor M. |
collection | PubMed |
description | Castration-resistant prostate cancer is the lethal form of prostate cancer and most commonly remains dependent on androgen receptor (AR) signaling. Current therapies use AR signaling inhibitors (ARSI) exemplified by abiraterone acetate, a P450c17 inhibitor, and enzalutamide, a potent AR antagonist. However, drug resistance to these agents occurs within 12-18 months and they only prolong overall survival by 3-4 months. Multiple mechanisms can contribute to ARSI drug resistance. These mechanisms can include but are not limited to germline mutations in the AR, post-transcriptional alterations in AR structure, and adaptive expression of genes involved in the intracrine biosynthesis and metabolism of androgens within the tumor. This review focuses on intracrine androgen biosynthesis, how this can contribute to ARSI drug resistance, and therapeutic strategies that can be used to surmount these resistance mechanisms. |
format | Online Article Text |
id | pubmed-8992556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | OAE Publishing Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89925562022-05-16 Intracrine androgen biosynthesis and drug resistance Penning, Trevor M. Asangani, Irfan A. Sprenger, Cynthia Plymate, Stephen Cancer Drug Resist Review Castration-resistant prostate cancer is the lethal form of prostate cancer and most commonly remains dependent on androgen receptor (AR) signaling. Current therapies use AR signaling inhibitors (ARSI) exemplified by abiraterone acetate, a P450c17 inhibitor, and enzalutamide, a potent AR antagonist. However, drug resistance to these agents occurs within 12-18 months and they only prolong overall survival by 3-4 months. Multiple mechanisms can contribute to ARSI drug resistance. These mechanisms can include but are not limited to germline mutations in the AR, post-transcriptional alterations in AR structure, and adaptive expression of genes involved in the intracrine biosynthesis and metabolism of androgens within the tumor. This review focuses on intracrine androgen biosynthesis, how this can contribute to ARSI drug resistance, and therapeutic strategies that can be used to surmount these resistance mechanisms. OAE Publishing Inc. 2020-11-03 /pmc/articles/PMC8992556/ /pubmed/35582223 http://dx.doi.org/10.20517/cdr.2020.60 Text en © The Author(s) 2020. https://creativecommons.org/licenses/by/4.0/© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Penning, Trevor M. Asangani, Irfan A. Sprenger, Cynthia Plymate, Stephen Intracrine androgen biosynthesis and drug resistance |
title | Intracrine androgen biosynthesis and drug resistance |
title_full | Intracrine androgen biosynthesis and drug resistance |
title_fullStr | Intracrine androgen biosynthesis and drug resistance |
title_full_unstemmed | Intracrine androgen biosynthesis and drug resistance |
title_short | Intracrine androgen biosynthesis and drug resistance |
title_sort | intracrine androgen biosynthesis and drug resistance |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992556/ https://www.ncbi.nlm.nih.gov/pubmed/35582223 http://dx.doi.org/10.20517/cdr.2020.60 |
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