scholarly journals Integrated multi‐omics data reveals the molecular subtypes and guides the androgen receptor signalling inhibitor treatment of prostate cancer

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Jialin Meng ◽  
Xiaofan Lu ◽  
Chen Jin ◽  
Yujie Zhou ◽  
Qintao Ge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Molecular Subtypes ◽  
Omics Data ◽  
Receptor Signalling ◽  
Inhibitor Treatment

scholarly journals Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Mohammad Asim ◽  
Firas Tarish ◽  
Heather I. Zecchini ◽  
Kumar Sanjiv ◽  
Eleni Gelali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Synthetic Lethality ◽  
Receptor Signalling

scholarly journals Androgen Receptor Signalling in Prostate Cancer: The Functional Consequences of Acetylation

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Derek N. Lavery ◽  
Charlotte L. Bevan
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Histone Deacetylases ◽  
Transcriptional Response ◽  
Fine Tuning ◽  
Receptor Signalling ◽  
Prostate Carcinogenesis ◽  
Functional Consequences

The androgen receptor (AR) is a ligand activated transcription factor and member of the steroid hormone receptor (SHR) subfamily of nuclear receptors. In the early stages of prostate carcinogenesis, tumour growth is dependent on androgens, and AR directly mediates these effects by modulating gene expression. During transcriptional regulation, the AR recruits numerous cofactors with acetylation-modifying enzymatic activity, the best studied include p300/CBP and the p160/SRC family of coactivators. It is known that recruitment of histone acetyltransferases (HATs) and histone deacetylases (HDACs) is key in fine-tuning responses to androgens and is thus likely to play a role in prostate cancer progression. Further, these proteins can also modify the AR itself. The functional consequences of AR acetylation, the role of modifying enzymes in relation to AR transcriptional response, and prostate cancer will be discussed.

scholarly journals Androgen receptor signalling inhibitors: post-chemotherapy, pre-chemotherapy and now in castration sensitive prostate cancer

2021 ◽  
Author(s):  
Nicholas Mitsiades ◽  
Salma Kaochar
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
The Past ◽  
Receptor Signalling ◽  
Combined Androgen Blockade ◽  
Clinical Resistance ◽  
Hormonal Therapies ◽  
Combination Regimens

Based on pioneering work by Huggins, Hodges and others, hormonal therapies have been established as an effective approach for advanced prostate cancer (PC) for the past 8 decades. However, it quickly became evident that androgen deprivation therapy (ADT) via surgical or medical castration accomplishes inadequate inhibition of the androgen receptor (AR) axis, with clinical resistance inevitably emerging due to adrenal and intratumoral sources of androgens and other mechanisms. Early efforts to augment ADT by adding adrenal-targeting agents (aminoglutethimide, ketoconazole) or AR antagonists (flutamide, bicalutamide, nilutamide, cyproterone) failed to achieve overall survival (OS) benefits, although they did exhibit some evidence of limited clinical activity. More recently, four new Androgen Receptor Signalling Inhibitors (ARSIs) successfully entered clinical practice. Specifically, the CYP17 inhibitor abiraterone acetate and the 2nd generation AR antagonists (enzalutamide, apalutamide and darolutamide) achieved OS benefits for PC patients, confirmed the importance of reactivated AR signaling in castration-resistant PC and validated important concepts that had been proposed in the field several decades ago but had remained so far unproven, including adrenal-targeted therapy and combined androgen blockade. The past decade has seen steady advances towards more comprehensive AR axis targeting. Now the question is raised whether we have accomplished the maximum AR axis inhibition possible or there is still room for improvement. This review, marking the 80-year anniversary of ADT and 10-year anniversary of successful ARSIs, examines their current clinical use and discusses future directions, in particular combination regimens, to maximize their efficacy, delay emergence of resistance and improve patient outcomes.

Improving the Outcome of Patients with Castration-resistant Prostate Cancer Through Rational Targeting of the Androgen Receptor

2009 ◽  
Vol 05 (01) ◽  
pp. 58
Author(s):  
Gerhardt Attard ◽  
Johann S De Bono ◽  
Chris Parker ◽  
◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Significant Proportion ◽  
Serum Levels ◽  
Castration Resistant Prostate Cancer ◽  
Common Cause ◽  
Receptor Signalling ◽  
Castration Resistant ◽  
Prostate Cancers ◽  
Related Mortality

Castration-resistant prostate cancer (CRPC) is now the second most common cause of male cancer-related mortality. Recent evidence confirms that androgen receptor signalling continues to drive a significant proportion of progressing prostate cancers despite castrate serum levels of testosterone and multiple hormonal interventions. An increased understanding of the molecular biology underlying CRPC is informing on therapeutic targets for this disease, and we hypothesise that this will lead to the development of more efficacious drugs.

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