scholarly journals Interaction between Non-Coding RNAs and Androgen Receptor with an Especial Focus on Prostate Cancer

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3198
Author(s):  
Mohammad Taheri ◽  
Tayyebeh Khoshbakht ◽  
Elena Jamali ◽  
Julia Kallenbach ◽  
Soudeh Ghafouri-Fard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Dna Binding ◽  
Treatment Options ◽  
Practical Importance ◽  
Circular Rnas ◽  
Expression Recognition ◽  
Terminal Domain ◽  
Treat Prostate Cancer ◽  
Non Coding Rnas

The androgen receptor (AR) is a member of the nuclear receptor superfamily and has three functional domains, namely the N-terminal, DNA binding, and C-terminal domain. The N-terminal domain harbors potent transactivation functions, whereas the C-terminal domain binds to androgens and antiandrogens used to treat prostate cancer. AR has genomic activity being DNA binding-dependent or through interaction with other DNA-bound transcription factors, as well as a number of non-genomic, non-canonical functions, such as the activation of the ERK, AKT, and MAPK pathways. A bulk of evidence indicates that non-coding RNAs have functional interactions with AR. This type of interaction is implicated in the pathogenesis of human malignancies, particularly prostate cancer. In the current review, we summarize the available data on the role of microRNAs, long non-coding RNAs, and circular RNAs on the expression of AR and modulation of AR signaling, as well as the effects of AR on their expression. Recognition of the complicated interaction between non-coding RNAs and AR has practical importance in the design of novel treatment options, as well as modulation of response to conventional therapeutics.

scholarly journals Development of an Androgen Receptor Inhibitor Targeting the N-Terminal Domain of Androgen Receptor for Treatment of Castration Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3488
Author(s):  
Fuqiang Ban ◽  
Eric Leblanc ◽  
Ayse Derya Cavga ◽  
Chia-Chi Flora Huang ◽  
Mark R. Flory ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Splice Variants ◽  
Full Length ◽  
Cancer Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Terminal Domain ◽  
Castration Resistant ◽  
Coregulatory Proteins ◽  
Androgen Binding

Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castration-resistant prostate cancer. Resistance can occur when mutations in the androgen receptor (AR) render anti-androgen drugs ineffective or through the expression of constitutively active splice variants lacking the androgen binding domain entirely (e.g., ARV7). In this study, we are reporting the discovery of a novel AR-NTD covalent inhibitor 1-chloro-3-[(5-([(2S)-3-chloro-2-hydroxypropyl]amino)naphthalen-1-yl)amino]propan-2-ol (VPC-220010) targeting the AR-N-terminal Domain (AR-NTD). VPC-220010 inhibits AR-mediated transcription of full length and truncated variant ARV7, downregulates AR response genes, and selectively reduces the growth of both full-length AR- and truncated AR-dependent prostate cancer cell lines. We show that VPC-220010 disrupts interactions between AR and known coactivators and coregulatory proteins, such as CHD4, FOXA1, ZMIZ1, and several SWI/SNF complex proteins. Taken together, our data suggest that VPC-220010 is a promising small molecule that can be further optimized into effective AR-NTD inhibitor for the treatment of CRPC.

scholarly journals AR Splicing Variants and Resistance to AR Targeting Agents

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2563
Author(s):  
Mayuko Kanayama ◽  
Changxue Lu ◽  
Jun Luo ◽  
Emmanuel S. Antonarakis
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Splice Variants ◽  
Treatment Options ◽  
Predictive Biomarker ◽  
Castration Resistant Prostate Cancer ◽  
Treatment Benefit ◽  
Novel Biomarkers ◽  
The Many ◽  
Preclinical And Clinical Studies

Over the past decade, advances in prostate cancer research have led to discovery and development of novel biomarkers and effective treatments. As treatment options diversify, it is critical to further develop and use optimal biomarkers for the purpose of maximizing treatment benefit and minimizing unwanted adverse effects. Because most treatments for prostate cancer target androgen receptor (AR) signaling, aberrations affecting this drug target are likely to emerge following the development of castration-resistant prostate cancer (CRPC), and it is conceivable that such aberrations may play a role in drug resistance. Among the many AR aberrations, we and others have been studying androgen receptor splice variants (AR-Vs), especially AR-V7, and have conducted preclinical and clinical studies to develop and validate the clinical utility of AR-V7 as a prognostic and potential predictive biomarker. In this review, we first describe mechanisms of AR-V generation, regulation and their functions from a molecular perspective. We then discuss AR-Vs from a clinical perspective, focusing on the significance of AR-Vs detected in different types of human specimens and AR-Vs as potential therapeutic targets.

scholarly journals MP79-04 THE PRECLINICAL CHARACTERIZATION AND DEVELOPMENT OF EPI-7386, AN N-TERMINAL DOMAIN ANDROGEN RECEPTOR INHIBITOR, FOR THE TREATMENT OF PROSTATE CANCER

2020 ◽  
Vol 203 ◽  
pp. e1216
Author(s):  
Ronan Le Moigne* ◽  
C. Adriana Banuelos ◽  
Nasrin R. Mawji ◽  
Teresa Tam ◽  
Jun Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Terminal Domain ◽  
Receptor Inhibitor

scholarly journals Hsp70 Binds to the Androgen Receptor N-terminal Domain and Modulates the Receptor Function in Prostate Cancer Cells

2018 ◽  
Vol 18 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Jun Dong ◽  
Zeyu Wu ◽  
Dan Wang ◽  
Laura E. Pascal ◽  
Joel B. Nelson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Receptor Function ◽  
Prostate Cancer Cells ◽  
Terminal Domain

scholarly journals Combination therapy with androgen receptor N‐terminal domain antagonist EPI‐7170 and enzalutamide yields synergistic activity in AR‐V7‐positive prostate cancer

2020 ◽  
Vol 14 (10) ◽  
pp. 2455-2470
Author(s):  
Yukiyoshi Hirayama ◽  
Teresa Tam ◽  
Kunzhong Jian ◽  
Raymond J. Andersen ◽  
Marianne D. Sadar
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Combination Therapy ◽  
Synergistic Activity ◽  
Terminal Domain

scholarly journals EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer

2019 ◽  
Vol 30 ◽  
pp. v189-v190 ◽  
Author(s):  
R Le Moigne ◽  
C.A. Banuelos ◽  
N.R. Mawji ◽  
T. Tam ◽  
J. Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Terminal Domain ◽  
Receptor Inhibitor

Interaction mechanism exploration of R-bicalutamide/S-1 with WT/W741L AR using molecular dynamics simulations

2015 ◽  
Vol 11 (12) ◽  
pp. 3347-3354 ◽  
Author(s):  
Hongli Liu ◽  
Xiaoli An ◽  
Shuyan Li ◽  
Yuwei Wang ◽  
Jiazhong Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Dynamics ◽  
Androgen Receptor ◽  
Molecular Dynamics Simulations ◽  
First Generation ◽  
Interaction Mechanism ◽  
Androgen Action ◽  
Treat Prostate Cancer ◽  
Dynamics Simulations

R-Bicalutamide is a first generation antiandrogen used to treat prostate cancer, which inhibits androgen action by competitively binding to the androgen receptor (AR).

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