Kim N Chi1, Amina Zoubeidi, Martin E Gleave. 1. The Prostate Centre at Vancouver General Hospital, 6th Floor, 2775 Laurel Street, Vancouver, V5Z 1M9, British Columbia, Canada.
Abstract
BACKGROUND: Clusterin is a stress-induced cytoprotective chaperone protein, regulated by HSF1, and functions similarly to a small heat-shock protein. Clusterin is expressed in a variety of cancers and associated with broad-spectrum treatment resistance. Custirsen (OGX-011) is a 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA; it is currently in clinical trials for patients with cancer. OBJECTIVE/ METHODS: To review the literature on the role of clusterin in cancer progression and treatment resistance, and to summarize completed and ongoing clinical trials with custirsen. RESULTS/ CONCLUSIONS: Custirsen is well tolerated in humans and biologically active in inhibiting expression of clusterin in patients with cancer. Randomized trials of custirsen in combination with chemotherapy are planned in patients with castration-resistant prostate cancer.
BACKGROUND:Clusterin is a stress-induced cytoprotective chaperone protein, regulated by HSF1, and functions similarly to a small heat-shock protein. Clusterin is expressed in a variety of cancers and associated with broad-spectrum treatment resistance. Custirsen (OGX-011) is a 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA; it is currently in clinical trials for patients with cancer. OBJECTIVE/ METHODS: To review the literature on the role of clusterin in cancer progression and treatment resistance, and to summarize completed and ongoing clinical trials with custirsen. RESULTS/ CONCLUSIONS: Custirsen is well tolerated in humans and biologically active in inhibiting expression of clusterin in patients with cancer. Randomized trials of custirsen in combination with chemotherapy are planned in patients with castration-resistant prostate cancer.
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