Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer

Transcriptional control of gene expression is fundamental to all cellular processes. Conversely, transcriptional dysregulation is a hallmark of cancer. While this hallmark is a key driver of all malignancy-related process, it also represents a vulnerability that can be exploited therapeutically. Pro...

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Main Authors: Razia Rahman, Luke A. Selth
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523325001093
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author Razia Rahman
Luke A. Selth
author_facet Razia Rahman
Luke A. Selth
author_sort Razia Rahman
collection DOAJ
description Transcriptional control of gene expression is fundamental to all cellular processes. Conversely, transcriptional dysregulation is a hallmark of cancer. While this hallmark is a key driver of all malignancy-related process, it also represents a vulnerability that can be exploited therapeutically. Prostate cancer is a prime example of this phenomenon: it is characterised by aberrant transcription and treated with drugs that influence transcriptional pathways. Indeed, the primary oncogenic driver and therapeutic target of prostate cancer, the androgen receptor (AR), is a transcription factor. Moreover, a plethora of other transcriptional regulators, including transcriptional cyclin-dependent kinases (CDK7, CDK8 and CDK9), MYC and Bromodomain-containing protein 4 (BRD4), play prominent roles in disease progression. In this review, we focus on the roles of transcriptional CDKs in prostate cancer growth, metastasis and therapy resistance and discuss their interplay with AR, MYC and BRD4. Additionally, we explore recent advances in the therapeutic targeting of transcriptional CDKs and propose how these strategies could be effectively harnessed for the treatment of prostate cancer.
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spelling doaj-art-90096ec9217a4328a2da2eff145d069e2025-08-20T02:15:51ZengElsevierTranslational Oncology1936-52332025-05-015510237810.1016/j.tranon.2025.102378Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancerRazia Rahman0Luke A. Selth1Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, South AustraliaFlinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, South Australia; Flinders University, Freemasons Centre for Male Health and Wellbeing, Adelaide, South Australia; Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia; Corresponding author at: Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, South Australia.Transcriptional control of gene expression is fundamental to all cellular processes. Conversely, transcriptional dysregulation is a hallmark of cancer. While this hallmark is a key driver of all malignancy-related process, it also represents a vulnerability that can be exploited therapeutically. Prostate cancer is a prime example of this phenomenon: it is characterised by aberrant transcription and treated with drugs that influence transcriptional pathways. Indeed, the primary oncogenic driver and therapeutic target of prostate cancer, the androgen receptor (AR), is a transcription factor. Moreover, a plethora of other transcriptional regulators, including transcriptional cyclin-dependent kinases (CDK7, CDK8 and CDK9), MYC and Bromodomain-containing protein 4 (BRD4), play prominent roles in disease progression. In this review, we focus on the roles of transcriptional CDKs in prostate cancer growth, metastasis and therapy resistance and discuss their interplay with AR, MYC and BRD4. Additionally, we explore recent advances in the therapeutic targeting of transcriptional CDKs and propose how these strategies could be effectively harnessed for the treatment of prostate cancer.http://www.sciencedirect.com/science/article/pii/S1936523325001093Prostate cancerCyclin-dependent kinaseAndrogen receptorTargeted therapiesTranscription
spellingShingle Razia Rahman
Luke A. Selth
Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer
Translational Oncology
Prostate cancer
Cyclin-dependent kinase
Androgen receptor
Targeted therapies
Transcription
title Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer
title_full Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer
title_fullStr Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer
title_full_unstemmed Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer
title_short Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer
title_sort cyclin dependent kinases as mediators of aberrant transcription in prostate cancer
topic Prostate cancer
Cyclin-dependent kinase
Androgen receptor
Targeted therapies
Transcription
url http://www.sciencedirect.com/science/article/pii/S1936523325001093
work_keys_str_mv AT raziarahman cyclindependentkinasesasmediatorsofaberranttranscriptioninprostatecancer
AT lukeaselth cyclindependentkinasesasmediatorsofaberranttranscriptioninprostatecancer