Abstract
Clusterin is a stress-induced cytoprotective chaperone that confers broad-spectrum treatment resistance and is overexpressed across a number of cancers. custirsen (OGX-011) is a promising novel second-generation antisense inhibitor of clusterin in clinical development. This article describes the mechanism of action and safety profile of OGX-011 and details the Phase I and II results in human solid organ malignancies. Two Phase III registration trials are currently under recruitment evaluating OGX-011 in combination with chemotherapy in patients with metastatic castration-resistant prostate cancer. These studies not only have the potential to significantly alter the standard of care in prostate cancer, but would also endorse a new class of targets and targeted therapy approach for cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Clinical Trials, Phase I as Topic
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Clinical Trials, Phase II as Topic
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Clinical Trials, Phase III as Topic
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Clusterin / antagonists & inhibitors*
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Clusterin / genetics
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Clusterin / metabolism
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Drug Approval
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Humans
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Male
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Oligonucleotides, Antisense* / administration & dosage
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Oligonucleotides, Antisense* / chemistry
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Oligonucleotides, Antisense* / pharmacokinetics
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Orchiectomy
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / pathology
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Thionucleotides / administration & dosage*
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Thionucleotides / adverse effects
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Thionucleotides / chemistry
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Thionucleotides / pharmacokinetics
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United States
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United States Food and Drug Administration
Substances
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Clusterin
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OGX-011
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Oligonucleotides, Antisense
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Thionucleotides