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Current status of androgen receptor-splice variant 7 inhibitor niclosamide in castrate-resistant prostate-cancer

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Summary

Castrate-Resistant Prostate-Cancer (CRPC) is one of the most common malignancies occurring in men. Unfortunately, even if several recently approved agents clinically improved the outcome of CRPC patients, none of these is curative especially for a splice version of the Androgen Receptor (AR) AR-V7, which is a variant of the receptor constitutively activated and does not require the presence of androgens for the activation AR down-stream pathways. Since high AR-V7 expression is one of the most common features of CRPC, targeting this receptor variant is considered as one of the most promising strategies for treating this disease. Therefore anti-AR-V7 molecules could lead to a potential shift in paradigm in the treatment of CRPC. Niclosamide, an already FDA-approved anti-helminthic drug, was identified as a potent AR-V7 inhibitor in prostate cancer cells. Due to the recent positive preclinical results, niclosamide may be an interesting and novel type of targeted treatments for CRPC. This mini-review outlines the most recent pre- and clinical- data on the current status of niclosamide in the treatment of ARV7-positive CRPC patients.

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Authors and Affiliations

  1. Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129, Trieste, Italy

    Navid Sobhani, Daniele Generali & Alberto D’Angelo

  2. Unit of molecular therapy and pharmacogenomic, AO Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100, Cremona, Italy

    Daniele Generali

  3. Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, via Padre Pio 1, 85028, Rionero in Vulture, PZ, Italy

    Michele Aieta & Giandomenico Roviello

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  1. Navid Sobhani
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Correspondence to Giandomenico Roviello.

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This article does not contain any studies with human participants or animals performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Sobhani, N., Generali, D., D’Angelo, A. et al. Current status of androgen receptor-splice variant 7 inhibitor niclosamide in castrate-resistant prostate-cancer. Invest New Drugs 36, 1133–1137 (2018). https://doi.org/10.1007/s10637-018-0653-2

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  • DOI: https://doi.org/10.1007/s10637-018-0653-2

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