Current status of androgen receptor-splice variant 7 inhibitor niclosamide in castrate-resistant prostate-cancer
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.
KeywordsCastrate-resistant prostate-Cancer Androgen receptor Androgen receptor splice variant 7 Niclosamide
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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.
For this type of study, formal consent is not required.
- 4.Kantoff PW et al (2010) Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. Engl J Med 3635Google Scholar
- 35.Matias PM, Donner P, Coelho R, Thomaz M, Peixoto C, Macedo S, Otto N, Joschko S, Scholz P, Wegg A, Bäsler S, Schäfer M, Egner U, Carrondo MA (2000) Structural evidence for ligand specificity in the binding domain of the human androgen receptor. J Biol Chem 275:26164–26171CrossRefPubMedGoogle Scholar
- 42.Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, Lotan TL, Zheng Q, de Marzo AM, Isaacs JT, Isaacs WB, Nadal R, Paller CJ, Denmeade SR, Carducci MA, Eisenberger MA, Luo J (2014) AR-V7 and resistance to Enzalutamide and Abiraterone in prostate Cancer. N Engl J Med 371:1028–1038CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Steinestel JAM, Luedeke M, Arndt A (2014) Detecting predictive androgen receptor modifications in circulating prostate cancer cells. Oncotarget. https://doi.org/10.18632/oncotarget.3925
- 44.Scher HI, Graf RP, Schreiber NA, McLaughlin B, Lu D, Louw J, Danila DC, Dugan L, Johnson A, Heller G, Fleisher M, Dittamore R (2017) Nuclear-specific AR-V7 protein localization is necessary to guide treatment selection in metastatic castration-resistant prostate Cancer. Eur Urol 71:874–882CrossRefPubMedGoogle Scholar
- 46.Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, Han M, Partin AW, Vessella RL, Isaacs WB, Bova GS, Luo J (2009) Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate Cancer. Cancer Res 69:16–22CrossRefPubMedPubMedCentralGoogle Scholar