Custirsen (OGX-011): a second-generation antisense inhibitor of clusterin in development for the treatment of prostate cancer

Future Oncol. 2012 Oct;8(10):1239-51. doi: 10.2217/fon.12.129.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Clusterin / antagonists & inhibitors*
  • Clusterin / genetics
  • Clusterin / metabolism
  • Drug Approval
  • Humans
  • Male
  • Oligonucleotides, Antisense* / administration & dosage
  • Oligonucleotides, Antisense* / chemistry
  • Oligonucleotides, Antisense* / pharmacokinetics
  • Orchiectomy
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Thionucleotides / administration & dosage*
  • Thionucleotides / adverse effects
  • Thionucleotides / chemistry
  • Thionucleotides / pharmacokinetics
  • United States
  • United States Food and Drug Administration

Substances

  • Clusterin
  • OGX-011
  • Oligonucleotides, Antisense
  • Thionucleotides