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Clusterin as a Target for Treatment of Castration-Resistant Prostate Cancer

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Androgen-Responsive Genes in Prostate Cancer

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Abstract

Secretory clusterin (sCLU) is a stress-induced cytoprotective ­molecular chaperone upregulated in an adaptive survival manner by various triggers to confer acquired treatment resistance. sCLU inhibits stress-induced apoptosis and induces epithelial mesenchymal transition by modulating pro-survival signaling and transcriptional networks. sCLU is associated with poor prognosis and treatment resistance including radiation, hormone, or chemotherapy. sCLU acts through an ATP-independent mechanism making this target less amenable to inhibition by small molecules, and so strategies to inhibit CLU at the gene expression level are required. In this chapter, we will review the rationale for targeting sCLU in castration-resistant prostate cancer (CRPC) and discuss the current status of preclinical and clinical studies using sCLU antisense (OGX-011) as a therapeutic target in CRPC.

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Authors and Affiliations

  1. The Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC, Canada, V6H 3Z6

    Amina Zoubeidi & Martin Gleave M.D. F.R.C.S.C., F.A.C.S.

  2. Department of Urological Sciences, University of British Columbia, Vancouver, BC, Canada

    Amina Zoubeidi & Martin Gleave M.D. F.R.C.S.C., F.A.C.S.

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  1. Amina Zoubeidi
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  2. Martin Gleave M.D. F.R.C.S.C., F.A.C.S.
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Correspondence to Martin Gleave M.D. F.R.C.S.C., F.A.C.S. .

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  1. , Shadyside Medical Center, University of Pittsburgh, Centre Ave 5200, Pittsburgh, 15232, Pennsylvania, USA

    Zhou Wang

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Zoubeidi, A., Gleave, M. (2013). Clusterin as a Target for Treatment of Castration-Resistant Prostate Cancer. In: Wang, Z. (eds) Androgen-Responsive Genes in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6182-1_20

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