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Potential use of custirsen to treat prostate cancer

Authors Higano CS

Received 19 March 2013

Accepted for publication 2 May 2013

Published 25 June 2013 Volume 2013:6 Pages 785—797

DOI https://doi.org/10.2147/OTT.S33077

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Celestia S Higano

Department of Medicine, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Abstract: Over the last few years, five agents have demonstrated a survival benefit over a comparator treatment or placebo in the treatment of metastatic castration-resistant prostate cancer and have been approved by the US Food and Drug Administration: sipuleucel-T (a dendritic cell immunotherapy); cabazitaxel; abiraterone acetate and enzalutamide (both hormonal agents); and radium 223 (an alpha emitter). The development of these agents pivoted on whether patients had been treated with docetaxel, which remains the first-line chemotherapy of choice. To date, no combination of docetaxel and another active agent has demonstrated superiority to docetaxel alone despite numerous Phase III trials. Clusterin is a cytoprotective chaperone protein that is upregulated in response to various anticancer therapies. When overexpressed, clusterin interferes with apoptotic signaling, thereby promoting cell survival and conferring broad-spectrum resistance in cancer cell lines. Custirsen (OGX-011) is a second-generation 2´-methoxyethyl modified phosphorothioate antisense oligonucleotide that inhibits expression of clusterin. This review presents the preclinical and clinical data that provided the rationale for the combination of custirsen with chemotherapy in ongoing Phase III trials.

Keywords: castration-resistant prostate cancer, clusterin, custirsen, OGX-011, antisense, OGX-427, apoptosis

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