Rodhan Patke
Epitranscriptomic mechanisms of androgen signalling and prostate cancer
Patke, Rodhan; Harris, Anna E.; Woodcock, Corinne L.; Thompson, Rachel; Santos, Rute; Kumari, Amber; Allegrucci, Cinzia; Archer, Nathan; Gudas, Lorraine J.; Robinson, Brian D.; Persson, Jenny L.; Fray, Rupert; Jeyapalan, Jennie; Rutland, Catrin S.; Rakha, Emad; Madhusudan, Srinivasan; Emes, Richard D.; Muyangwa-Semenova, Musalwa; Alsaleem, Mansour; de Brot, Simone; Green, William; Ratan, Hari; Mongan, Nigel P.; Lothion-Roy, Jennifer
Authors
ANNA HARRIS Anna.Harris@nottingham.ac.uk
Research Fellow
CORINNE WOODCOCK Corinne.Woodcock1@nottingham.ac.uk
Research Fellow
Rachel Thompson
Rute Santos
Amber Kumari
CINZIA ALLEGRUCCI cinzia.allegrucci@nottingham.ac.uk
Associate Professor
NATHAN ARCHER Nathan.Archer@nottingham.ac.uk
Assistant Professor
Lorraine J. Gudas
Brian D. Robinson
Jenny L. Persson
RUPERT FRAY RUPERT.FRAY@NOTTINGHAM.AC.UK
Professor of Epitranscriptomics
Dr JENNIE JEYAPALAN jennie.jeyapalan@nottingham.ac.uk
Assistant Professor
CATRIN RUTLAND CATRIN.RUTLAND@NOTTINGHAM.AC.UK
Professor of Molecular Medicine
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
SRINIVASAN MADHUSUDAN srinivasan.madhusudan@nottingham.ac.uk
Professor of Medical Oncology
Richard D. Emes
Musalwa Muyangwa-Semenova
Mansour Alsaleem
Simone de Brot
William Green
Hari Ratan
NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Professor of Oncology
JENNY LOTHION-ROY JENNY.LOTHION-ROY@NOTTINGHAM.AC.UK
Clinical Assistant Professor
Abstract
Prostate cancer (PCa) is the second most common cancer diagnosed in men. While radical prostatectomy and radiotherapy are often successful in treating localised disease, post-treatment recurrence is common. As the androgen receptor (AR) and androgen hormones play an essential role in prostate carcinogenesis and progression, androgen deprivation therapy (ADT) is often used to deprive PCa cells of the pro-proliferative effect of androgens. ADTs act by either blocking androgen biosynthesis (e.g. abiraterone) or blocking AR function (e.g. bicalutamide, enzalutamide, apalutamide, darolutamide). ADT is often effective in initially suppressing PCa growth and progression, yet emergence of castrate-resistant PCa and progression to neuroendocrine-like PCa following ADT are major clinical challenges. For this reason, there is an urgent need to identify novel approaches to modulate androgen signalling to impede PCa progression whilst also preventing or delaying therapy resistance. The mechanistic convergence of androgen and epitranscriptomic signalling offers a potential novel approach to treat PCa. The epitranscriptome involves covalent modifications of mRNA, notably, in the context of this review, the N(6)-methyladenosine (m6A) modification. m6A is involved in the regulation of mRNA splicing, stability, and translation, and has recently been shown to play a role in PCa and androgen signalling. The m6A modification is dynamically regulated by the METTL3-containing methyltransferase complex, and the FTO and ALKBH5 RNA demethylases. Given the need for novel approaches to treat PCa, there is significant interest in new therapies that target m6A that modulate AR expression and androgen signalling. This review critically summarises the potential benefit of such epitranscriptomic therapies for PCa patients.
Citation
Patke, R., Harris, A. E., Woodcock, C. L., Thompson, R., Santos, R., Kumari, A., Allegrucci, C., Archer, N., Gudas, L. J., Robinson, B. D., Persson, J. L., Fray, R., Jeyapalan, J., Rutland, C. S., Rakha, E., Madhusudan, S., Emes, R. D., Muyangwa-Semenova, M., Alsaleem, M., de Brot, S., …Lothion-Roy, J. (2024). Epitranscriptomic mechanisms of androgen signalling and prostate cancer. Neoplasia, 56, Article 101032. https://doi.org/10.1016/j.neo.2024.101032
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 15, 2024 |
Online Publication Date | Jul 20, 2024 |
Publication Date | 2024-10 |
Deposit Date | Aug 29, 2024 |
Publicly Available Date | Sep 4, 2024 |
Journal | Neoplasia |
Print ISSN | 1522-8002 |
Electronic ISSN | 1476-5586 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 56 |
Article Number | 101032 |
DOI | https://doi.org/10.1016/j.neo.2024.101032 |
Public URL | https://nottingham-repository.worktribe.com/output/37604077 |
Publisher URL | https://www.sciencedirect.com/science/article/pii/S1476558624000745?via%3Dihub |
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