The Adrenal Androgen Androstenediol Is Present in Prostate Cancer Tissue after Androgen Deprivation Therapy and Activates Mutated Androgen Receptor

2004 ◽  
Vol 64 (2) ◽  
pp. 765-771 ◽  
Author(s):  
Atsushi Mizokami ◽  
Eitetsu Koh ◽  
Hiroshi Fujita ◽  
Yuji Maeda ◽  
Masayuki Egawa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Cancer Tissue ◽  
Adrenal Androgen ◽  
Prostate Cancer Tissue

scholarly journals Androgen-regulated transcription ofESRP2drives alternative splicing patterns in prostate cancer

2019 ◽  
Author(s):  
Jennifer Munkley ◽  
Li Ling ◽  
S R Gokul Krishnan ◽  
Gerald Hysenaj ◽  
Emma Scott ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Disease Progression ◽  
Androgen Deprivation Therapy ◽  
Ectopic Expression ◽  
Androgen Deprivation ◽  
Cancer Tissue ◽  
List Type ◽  
Mrna Isoforms ◽  
Splice Isoform

AbstractProstate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulatorESRP2. BothESRP2and its close paralogESRP1are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including a key splicing switch in the metastatic regulatorFLNBwhich is associated with disease relapse.ESRP2expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this,FLNBsplicing was reciprocally switched by the AR antagonist bicalutamide (Casodex®). Our data reveal a new mechanism of splicing control in prostate cancer with important implications for metastatic disease progression.Key pointsTranscriptional regulation of ESRP2 by the androgen receptor controls splice isoform patterns in prostate cancer cells.Splicing switches regulated by the androgen-ESRP2 axis include a splice isoform in theFLNBgene that is a known metastatic driver.Both ESRP1 and ESRP2 are highly expressed in prostate cancer tissue.Ectopic expression of ESRP1 and 2 inhibits prostate cancer cell growth.By repressing ESRP2 expression androgen deprivation therapy (ADT) may dampen epithelial splicing programmes to inadvertently prime disease progression towards metastasis.

scholarly journals Next-generation androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592097813
Author(s):  
Pernelle Lavaud ◽  
Clément Dumont ◽  
Constance Thibault ◽  
Laurence Albiges ◽  
Giulia Baciarello ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Next Generation ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Recent Advances

Until recently, continuing androgen deprivation therapy (ADT) and closely monitoring patients until evolution towards metastatic castration-resistant prostate cancer (CRPC) were recommended in men with non-metastatic CRPC (nmCRPC). Because delaying the development of metastases and symptoms in these patients is a major issue, several trials have investigated next-generation androgen receptor (AR) axis inhibitors such as apalutamide, darolutamide, and enzalutamide in this setting. This review summarizes the recent advances in the management of nmCRPC, highlighting the favourable impact of next-generation AR inhibitors on metastases-free survival, overall survival and other clinically meaningful endpoints.

scholarly journals Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

Oncogene ◽  
2010 ◽  
Vol 29 (25) ◽  
pp. 3593-3604 ◽  
Author(s):  
Y Niu ◽  
T-M Chang ◽  
S Yeh ◽  
W-L Ma ◽  
Y Z Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation

Degradation of Androgen Receptor through Small Molecules for Prostate Cancer

2018 ◽  
Vol 18 (7) ◽  
pp. 652-667 ◽  
Author(s):  
Raoling Ge ◽  
Xi Xu ◽  
Pengfei Xu ◽  
Lei Li ◽  
Zhiyu Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Small Molecules ◽  
Androgen Deprivation Therapy ◽  
Resistance Mechanism ◽  
Androgen Deprivation ◽  
High Expression ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Androgen Receptor Antagonists

Prostate cancer is the most common carcinoma among aged males in western countries and more aggressive and lethal castration resistant prostate cancer often occurs after androgen deprivation therapy. The high expression of androgens and androgen receptor is closely related to prostate cancer. Efficient androgen receptor antagonists, such as enzalutamide and ARN-509, could be employed as potent anti-prostate cancer agents. Nevertheless, recent studies have revealed that F876L mutation in androgen receptor converts the action of enzalutamide and ARN-509 from an antagonist to agonist, so that novel strategies are urgent to address this resistance mechanism. In this review, we focus on the discussion about some novel strategies, which targets androgen receptor mainly through the degrading pathway as potential treatments for prostate cancer.

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