AR-V7 in Metastatic Prostate Cancer: A Strategy beyond Redemption
Navid Sobhani1, Praveen Kumar Neeli1, Alberto D'Angelo2
1Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
Metastatic prostate cancer is the most common cancer in males and the fifth cause of cancer mortality worldwide. Despite the major progress in this field, leading to the approval of novel anti-androgens, the prognosis is still poor. A significant number of patients acquire an androgen receptor splice variant 7 (AR-V7), which is constitutively activated and lacks the ligand-binding domain (LBD) while maintaining the nuclear localization signal and DNA-binding domain (DBD). This conformational change, even in the absence of the ligand, allows its retention within the nucleus, where it acts as a transcription factor repressing crucial tumor suppressor genes. AR-V7 is an important oncogenic driver and plays a role as an early diagnostic and prognostic marker, as well as a therapeutic target for antagonists such as niclosamide and TAS3681. Anti-AR-V7 drugs have shown promise in recent clinical investigations on this subset of patients. This mini-review focuses on the relevance of AR-V7 in the clinical manifestations of castration-resistant prostate cancer (CRPC) and summarizes redemptive therapeutic strategies.
Insights
Androgen receptor splice variant 7 (AR-V7) drives metastatic prostate cancer progression. Targeting AR-V7 offers a promising therapeutic strategy for castration-resistant prostate cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic prostate cancer (PCa) remains a leading cause of cancer mortality worldwide.
- Novel anti-androgen therapies have improved outcomes, but resistance remains a significant challenge.
- The androgen receptor splice variant 7 (AR-V7) is a key driver of resistance and progression in PCa.
Purpose of the Study:
- To review the role of AR-V7 in the clinical progression of castration-resistant prostate cancer (CRPC).
- To summarize emerging therapeutic strategies targeting AR-V7.
- To highlight AR-V7 as a diagnostic and prognostic marker.
Main Methods:
- Literature review of studies investigating AR-V7 in prostate cancer.
- Analysis of AR-V7's molecular mechanisms and clinical implications.
- Summary of preclinical and clinical data on AR-V7 antagonists.
Main Results:
- AR-V7 is constitutively active, lacking the ligand-binding domain, leading to nuclear retention and repression of tumor suppressor genes.
- AR-V7 expression is associated with poor prognosis and resistance to standard therapies.
- Emerging AR-V7 antagonists, including niclosamide and TAS3681, show therapeutic promise.
Conclusions:
- AR-V7 is a critical oncogenic driver in CRPC.
- Targeting AR-V7 represents a viable therapeutic approach for a subset of prostate cancer patients.
- Further clinical investigation of anti-AR-V7 therapies is warranted.
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