期刊
EXPERT OPINION ON INVESTIGATIONAL DRUGS
卷 17, 期 12, 页码 1955-1962出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543780802528609
关键词
antisense oligonucleotide; cancer; clusterin; custirsen; 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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