Related Experiment Video
Updated: Dec 27, 2025
Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
Published on: April 27, 2018
Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations
Changxue Lu1, Landon C Brown2, Emmanuel S Antonarakis1,3
1Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background:
The androgen receptor (AR) is a key prostate cancer drug target. Suppression of AR signaling mediated by the full-length AR (AR-FL) is the therapeutic goal of all existing AR-directed therapies. AR-targeting agents impart therapeutic benefit, but lead to AR aberrations that underlie disease progression and therapeutic resistance. Among the AR aberrations specific to castration-resistant prostate cancer (CRPC), AR variants (AR-Vs) have emerged as important indicators of disease progression and therapeutic resistance.
Methods:
We conducted a systemic review of the literature focusing on recent laboratory studies on AR-Vs following our last review article published in 2016. Topics ranged from measurement and detection, molecular origin, regulation, genomic function, and preclinical therapeutic targeting of AR-Vs. We provide expert opinions and perspectives on these topics.
Results:
Transcript sequences for 22 AR-Vs have been reported in the literature. Different AR-Vs may arise through different mechanisms, and can be regulated by splicing factors and dictated by genomic rearrangements, but a low-androgen environment is a prerequisite for generation of AR-Vs. The unique transcript structures allowed development of in situ and in-solution measurement and detection methods, including mRNA and protein detection, in both tissue and blood specimens. AR-V7 remains the main measurement target and the most extensively characterized AR-V. Although AR-V7 coexists with AR-FL, genomic functions mediated by AR-V7 do not require the presence of AR-FL. The distinct cistromes and transcriptional programs directed by AR-V7 and their coregulators are consistent with genomic features of progressive disease in a low-androgen environment. Preclinical development of AR-V-directed agents currently focuses on suppression of mRNA expression and protein degradation as well as targeting of the amino-terminal domain.
Conclusions:
Current literature continues to support AR-Vs as biomarkers and therapeutic targets in prostate cancer. Laboratory investigations reveal both challenges and opportunities in targeting AR-Vs to overcome resistance to current AR-directed therapies.
Insights
Androgen receptor variants (AR-Vs) are key to understanding and overcoming resistance in prostate cancer. Research highlights AR-Vs as crucial biomarkers and therapeutic targets, offering new strategies against advanced disease.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The androgen receptor (AR) is a primary target in prostate cancer therapy.
- Current treatments aim to suppress AR signaling but can lead to resistance via AR aberrations.
- Androgen receptor variants (AR-Vs) are critical indicators of castration-resistant prostate cancer (CRPC) progression and treatment resistance.
Purpose of the Study:
- To systematically review recent laboratory studies on AR variants (AR-Vs) since 2016.
- To provide expert perspectives on AR-V detection, origin, regulation, function, and therapeutic targeting.
- To explore challenges and opportunities in targeting AR-Vs for overcoming treatment resistance.
Main Methods:
- Systematic literature review of laboratory studies on AR variants.
- Focus on topics including measurement, detection, molecular origin, regulation, genomic function, and preclinical targeting.
- Inclusion of expert opinions and perspectives.
Main Results:
- 22 AR-V transcript sequences have been reported, arising through diverse mechanisms.
- AR-V generation requires a low-androgen environment and can be influenced by splicing factors and genomic rearrangements.
- AR-V7 is the most studied variant; its distinct genomic functions can operate independently of full-length AR (AR-FL) and are linked to progressive disease.
Conclusions:
- AR variants are validated biomarkers and therapeutic targets in prostate cancer.
- Laboratory research continues to uncover both challenges and potential strategies for targeting AR-Vs.
- Targeting AR-Vs offers a promising avenue to overcome resistance to current AR-directed therapies.
More Related Videos
12:13Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
07:25A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018