scholarly journals Recent Advances in Androgen-Receptor Splicing Variants Related to the Mechanism and Treatment of Castration-Resistant Prostate Cancer

2020 ◽  
Vol 9 (04) ◽  
pp. 9-12
Author(s):  
Jianguo Liao ◽  
Wenhai Pan
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Recent Advances ◽  
Splicing Variants

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 Emerging data on androgen receptor splice variants in prostate cancer

2016 ◽  
Vol 23 (12) ◽  
pp. T199-T210 ◽  
Author(s):  
Subing Cao ◽  
Yang Zhan ◽  
Yan Dong
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Splice Variants ◽  
Deep Understanding ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Splicing Variants ◽  
Current Therapies ◽  
Alternatively Spliced ◽  
Androgen Receptor Splice Variants

Androgen receptor splice variants are alternatively spliced variants of androgen receptor, which are C-terminally truncated and lack the canonical ligand-binding domain. Accumulating evidence has indicated a significant role of androgen receptor splice variants in mediating resistance of castration-resistant prostate cancer to current therapies and in predicting therapeutic responses. As such, there is an urgent need to target androgen receptor splicing variants for more effective treatment of castration-resistant prostate cancer. Identification of precise and critical targeting points to deactivate androgen receptor splicing variants relies on a deep understanding of how they are generated and the mechanisms of their action. In this review, we will focus on the emerging data on their generation, clinical significance and mechanisms of action as well as the therapeutic influence of these findings.

scholarly journals Castration-Resistant Prostate Cancer Refractory to Second-Generation Androgen Receptor Axis-Targeted Agents: Opportunities and Challenges

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 345 ◽  
Author(s):  
Yuki Kita ◽  
Takayuki Goto ◽  
Shusuke Akamatsu ◽  
Toshinari Yamasaki ◽  
Takahiro Inoue ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Second Generation ◽  
Considerable Proportion ◽  
Castration Resistant Prostate Cancer ◽  
Nonsense Mutations ◽  
Post Translational Modifications ◽  
Downstream Signaling ◽  
Castration Resistant ◽  
Splicing Variants

Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone and enzalutamide, enable stronger blockade of the androgen receptor (AR) axis and longer survival of men with castration-resistant prostate cancer (CRPC). However, the extent of the improved survival remains insufficient and the majority of patients eventually develop resistance to these novel agents. Some patients develop resistance against ARAT treatment through mechanisms termed “complete AR independence” or “AR indifference”, and no longer require activation of the AR axis. However, a considerable proportion of CRPC patients remain persistently dependent on AR or its downstream signaling pathways. Ligand-independent activation of the AR, an AR axis-dependent mechanism, is mediated by truncated forms of ARs that lack the ligand-binding domain (LBD), arising as products of AR splicing variants or nonsense mutations of AR. Post-translational modifications of ARs can also contribute to ligand-independent transactivation of the AR. Other mechanisms for AR axis activation are mediated by pathways that bypass the AR. Recent studies revealed that the glucocorticoid receptor can upregulate a similar transcription program to that of the AR, thus bypassing the AR. ARAT agents are essentially ineffective for CRPC driven by these AR-independent mechanisms. This review article describes recent efforts to overcome these refractory machineries for the development of next-generation AR axis blockade in CRPC.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

scholarly journals Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide

2017 ◽  
Vol 28 (9) ◽  
pp. 2264-2271 ◽  
Author(s):  
D.E. Rathkopf ◽  
M.R. Smith ◽  
C.J. Ryan ◽  
W.R. Berry ◽  
N.D. Shore ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
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