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The potential of clusterin inhibiting antisense oligodeoxynucleotide therapy for prostate cancer

Hideaki Miyake1, Isao Hara, Masato Fujisawa

  • 1Hyogo Medical Center for Adults, Department of Urology, 13-70 Kitaohji-cho, Akashi 673-8558, Japan. hideakimiyake@hotmail.com

Expert Opinion on Investigational Drugs
|April 26, 2006
PubMed

Insights

Antisense oligodeoxynucleotide (AS ODN) therapy targeting clusterin shows promise for prostate cancer treatment. Clinical trials indicate AS clusterin ODN (OGX-011) effectively suppresses tumor growth and enhances apoptosis, suggesting a novel therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Therapy

Background:

  • Clusterin is a cytoprotective gene that promotes resistance to apoptosis in prostate cancer.
  • Targeting clusterin offers a potential strategy to overcome treatment resistance.

Purpose of the Study:

  • To review the development of antisense oligodeoxynucleotide (AS ODN) therapy targeting clusterin for prostate cancer.
  • To evaluate the efficacy of AS clusterin ODN (OGX-011) in preclinical and clinical settings.

Main Methods:

  • Development of AS ODN to silence clusterin expression.
  • In vitro studies demonstrating clusterin's role in resistance.
  • In vivo studies using prostate cancer xenograft models.
  • Phase I clinical trials to determine optimal dosage and safety of OGX-011.

Main Results:

  • Silencing clusterin expression synergistically enhanced apoptosis induction with conventional therapies in xenograft models.
  • Phase I trials determined an optimal dose of OGX-011 for significant clusterin suppression in human prostate cancer tissue (

Conclusions:

  • AS ODN technology targeting clusterin represents a novel therapeutic strategy for prostate cancer.
  • Ongoing Phase II trials are evaluating OGX-011 efficacy in prostate, breast, and lung cancers.

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