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Review
. 2021 May 24;22(11):5515.
doi: 10.3390/ijms22115515.

AR-V7 in Metastatic Prostate Cancer: A Strategy beyond Redemption

Navid Sobhani  1 , Praveen Kumar Neeli  1 , Alberto D'Angelo  2 , Matteo Pittacolo  1 , Marianna Sirico  3   4 , Ilaria Camilla Galli  5 , Giandomenico Roviello  6 , Gabriella Nesi  6
Affiliations
Review

AR-V7 in Metastatic Prostate Cancer: A Strategy beyond Redemption

Navid Sobhani et al. Int J Mol Sci. .

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.

Keywords: AR-V7 antagonists; androgen receptor; androgen receptor splice variant 7; castration-resistant prostate cancer; niclosamide.

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Conflict of interest statement

The authors declare no conflict of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
Transcript structures for the full-length androgen receptor (AR-FL) and splice variant AR-V7.
Figure 2
Figure 2
Molecular pathways of AR-V7 antagonists on full-length androgen receptor (AR-FL) and AR-V7.
See this image and copyright information in PMC

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