scholarly journals Interplay between the androgen receptor signaling axis and microRNAs in prostate cancer

2019 ◽  
Vol 26 (5) ◽  
pp. R237-R257 ◽  
Author(s):  
Rayzel C Fernandes ◽  
Theresa E Hickey ◽  
Wayne D Tilley ◽  
Luke A Selth
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Transcription Factor ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Clinical Applications ◽  
Cancer Growth ◽  
Androgen Receptor Signaling ◽  
Resistance To Therapy ◽  
Signaling Axis

The androgen receptor (AR) is a ligand-activated transcription factor that drives prostate cancer. Since therapies that target the AR are the mainstay treatment for men with metastatic disease, it is essential to understand the molecular mechanisms underlying oncogenic AR signaling in the prostate. miRNAs are small, non-coding regulators of gene expression that play a key role in prostate cancer and are increasingly recognized as targets or modulators of the AR signaling axis. In this review, we examine the regulation of AR signaling by miRNAs and vice versa and discuss how this interplay influences prostate cancer growth, metastasis and resistance to therapy. Finally, we explore the potential clinical applications of miRNAs implicated in the regulation of AR signaling in this prevalent hormone-driven disease.

scholarly journals Loss and revival of androgen receptor signaling in advanced prostate cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Nicolò Formaggio ◽  
Mark A. Rubin ◽  
Jean-Philippe Theurillat
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Poor Prognosis ◽  
Advanced Prostate Cancer ◽  
Molecular Mechanisms ◽  
Androgen Receptor Signaling ◽  
Androgen Synthesis ◽  
Prostate Cancer Therapy ◽  
Signaling Axis ◽  
Prostate Cancers

AbstractTargeting the androgen receptor (AR) signaling axis has been, over decades, the mainstay of prostate cancer therapy. More potent inhibitors of androgen synthesis and antiandrogens have emerged and have been successfully implemented in clinical practice. That said, the stronger inhibition of the AR signaling axis has led in recent years to an increase of prostate cancers that de-differentiate into AR-negative disease. Unfortunately, this process is intimately linked with a poor prognosis. Here, we review the molecular mechanisms that enable cancer cells to switch from an AR-positive to an AR-negative disease and efforts to prevent/revert this process and thereby maintain/restore AR-dependence.

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.

A circulating tumor cell RNA assay for dynamic assessment of androgen receptor signaling inhibitors sensitivity in metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 157-157
Author(s):  
Yu Jen Jan ◽  
Junhee Yoon ◽  
Jie-Fu Chen ◽  
Pin-Jung Chen ◽  
Pai-Chi Teng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Dynamic Assessment ◽  
Receptor Signaling ◽  
Z Score ◽  
Androgen Receptor Signaling ◽  
Clinical Behavior ◽  
Gene Signatures ◽  
Signaling Inhibitors

157 Background: Tissue-based gene signatures can predict clinical behavior in prostate cancer (PC). Our objective was to extend their application to circulating tumor cells (CTCs) and to show that changes in the signature were associated with changes in clinical behavior. Methods: Our approach combined the Thermoresponsive(TR)-NanoVelcro CTC purification system with the Nanostring nCounter system for cellular purification and transcriptomic analysis. The Prostate Cancer Classification System (PCS) panel was modified for use in CTCs. We selected 31 blood samples from 23 PC patients receiving androgen receptor signaling inhibitors (ARSI) and measured the PCS1 Z score (probability). These findings were compared with clinical outcome data (responsiveness/resistance). Results: A modified, 16-gene PCS1 signature was established and validated through a rigorous bioinformatics process. We performed analytical validation of our combined CTC-RNA system to ensure reproducibility and specificity. In patient bloods, ARSI-resistant samples (ARSI-R, n = 14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n = 17) (Rank-sum test, P = 0.003). The analyzed bloods contained samples from 8 patients who developed resistance to an ARSI allowing for dynamic measurement of gene expression. Our analysis found that the PCS1 Z score increased at the time that ARSI-resistance emerged (Pairwise T-test, P = 0.016). Conclusions: Using this new methodology, contemporary, clinically-relevant gene signatures such as PCS could be measured non-invasively in CTCs. These findings can be used to relate gene expression to clinical drug response. This approach also allowed for measurement of dynamic variations of gene expression in individual patients over time that correlated to ARSI sensitivity.

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