Custirsen (OGX-011): A Second-Generation Antisense Inhibitor of Clusterin in Development for the Treatment of Prostate Cancer

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.

Keywords:

• antisense oligonucleotide
• cancer
• chaperone protein
• clusterin
• custirsen
• prostate cancer

Financial & competing interests disclosure

R Zielinski is supported by a BJ Amos scholarship from Westmead Hospital, Sydney, Australia. K Chi received research funding from OncoGenex Technologies Inc. and is a consultant for Janssen, Astellas, Medivation, Bayer and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

R Zielinski is supported by a BJ Amos scholarship from Westmead Hospital, Sydney, Australia. K Chi received research funding from OncoGenex Technologies Inc. and is a consultant for Janssen, Astellas, Medivation, Bayer and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.