Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies

Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apaluta...

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Autores principales:	Aasems Jacob, Rishi Raj, Derek B. Allison, Zin W. Myint
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostate cancer castrate-resistant growth metastases androgen receptor glucocorticoid receptor cytokines Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/be6b500cf3f34a71965605d8b1c7087c
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spelling	oai:doaj.org-article:be6b500cf3f34a71965605d8b1c7087c2021-11-11T15:30:50ZAndrogen Receptor Signaling in Prostate Cancer and Therapeutic Strategies10.3390/cancers132154172072-6694https://doaj.org/article/be6b500cf3f34a71965605d8b1c7087c2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5417https://doaj.org/toc/2072-6694Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.Aasems JacobRishi RajDerek B. AllisonZin W. MyintMDPI AGarticleprostate cancercastrate-resistant growthmetastasesandrogen receptorglucocorticoid receptorcytokinesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5417, p 5417 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate cancer castrate-resistant growth metastases androgen receptor glucocorticoid receptor cytokines Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	prostate cancer castrate-resistant growth metastases androgen receptor glucocorticoid receptor cytokines Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Aasems Jacob Rishi Raj Derek B. Allison Zin W. Myint Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies
description	Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.
format	article
author	Aasems Jacob Rishi Raj Derek B. Allison Zin W. Myint
author_facet	Aasems Jacob Rishi Raj Derek B. Allison Zin W. Myint
author_sort	Aasems Jacob
title	Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies
title_short	Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies
title_full	Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies
title_fullStr	Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies
title_full_unstemmed	Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies
title_sort	androgen receptor signaling in prostate cancer and therapeutic strategies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/be6b500cf3f34a71965605d8b1c7087c
work_keys_str_mv	AT aasemsjacob androgenreceptorsignalinginprostatecancerandtherapeuticstrategies AT rishiraj androgenreceptorsignalinginprostatecancerandtherapeuticstrategies AT derekballison androgenreceptorsignalinginprostatecancerandtherapeuticstrategies AT zinwmyint androgenreceptorsignalinginprostatecancerandtherapeuticstrategies
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Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies

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