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Targeting Prostate Cancer, the ‘Tousled Way’
Androgen deprivation therapy (ADT) has been the mainstay of prostate cancer (PCa) treatment, with success in developing more effective inhibitors of androgen synthesis and antiandrogens in clinical practice. However, hormone deprivation and AR ablation have caused an increase in ADT-insensitive PCas...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341820/ https://www.ncbi.nlm.nih.gov/pubmed/37446279 http://dx.doi.org/10.3390/ijms241311100 |
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author | Bhoir, Siddhant Benedetti, Arrigo De |
author_facet | Bhoir, Siddhant Benedetti, Arrigo De |
author_sort | Bhoir, Siddhant |
collection | PubMed |
description | Androgen deprivation therapy (ADT) has been the mainstay of prostate cancer (PCa) treatment, with success in developing more effective inhibitors of androgen synthesis and antiandrogens in clinical practice. However, hormone deprivation and AR ablation have caused an increase in ADT-insensitive PCas associated with a poor prognosis. Resistance to ADT arises through various mechanisms, and most castration-resistant PCas still rely on the androgen axis, while others become truly androgen receptor (AR)-independent. Our research identified the human tousled-like kinase 1 (TLK1) as a crucial early mediator of PCa cell adaptation to ADT, promoting androgen-independent growth, inhibiting apoptosis, and facilitating cell motility and metastasis. Although explicit, the growing role of TLK1 biology in PCa has remained underrepresented and elusive. In this review, we aim to highlight the diverse functions of TLK1 in PCa, shed light on the molecular mechanisms underlying the transition from androgen-sensitive (AS) to an androgen-insensitive (AI) disease mediated by TLK1, and explore potential strategies to counteract this process. Targeting TLK1 and its associated signaling could prevent PCa progression to the incurable metastatic castration-resistant PCa (mCRPC) stage and provide a promising approach to treating PCa. |
format | Online Article Text |
id | pubmed-10341820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103418202023-07-14 Targeting Prostate Cancer, the ‘Tousled Way’ Bhoir, Siddhant Benedetti, Arrigo De Int J Mol Sci Review Androgen deprivation therapy (ADT) has been the mainstay of prostate cancer (PCa) treatment, with success in developing more effective inhibitors of androgen synthesis and antiandrogens in clinical practice. However, hormone deprivation and AR ablation have caused an increase in ADT-insensitive PCas associated with a poor prognosis. Resistance to ADT arises through various mechanisms, and most castration-resistant PCas still rely on the androgen axis, while others become truly androgen receptor (AR)-independent. Our research identified the human tousled-like kinase 1 (TLK1) as a crucial early mediator of PCa cell adaptation to ADT, promoting androgen-independent growth, inhibiting apoptosis, and facilitating cell motility and metastasis. Although explicit, the growing role of TLK1 biology in PCa has remained underrepresented and elusive. In this review, we aim to highlight the diverse functions of TLK1 in PCa, shed light on the molecular mechanisms underlying the transition from androgen-sensitive (AS) to an androgen-insensitive (AI) disease mediated by TLK1, and explore potential strategies to counteract this process. Targeting TLK1 and its associated signaling could prevent PCa progression to the incurable metastatic castration-resistant PCa (mCRPC) stage and provide a promising approach to treating PCa. MDPI 2023-07-05 /pmc/articles/PMC10341820/ /pubmed/37446279 http://dx.doi.org/10.3390/ijms241311100 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Bhoir, Siddhant Benedetti, Arrigo De Targeting Prostate Cancer, the ‘Tousled Way’ |
title | Targeting Prostate Cancer, the ‘Tousled Way’ |
title_full | Targeting Prostate Cancer, the ‘Tousled Way’ |
title_fullStr | Targeting Prostate Cancer, the ‘Tousled Way’ |
title_full_unstemmed | Targeting Prostate Cancer, the ‘Tousled Way’ |
title_short | Targeting Prostate Cancer, the ‘Tousled Way’ |
title_sort | targeting prostate cancer, the ‘tousled way’ |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341820/ https://www.ncbi.nlm.nih.gov/pubmed/37446279 http://dx.doi.org/10.3390/ijms241311100 |
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