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Related Experiment Videos

Antisense strategies for oncogene inactivation.

C A Stein1, Luba Benimetskaya, S Mani

  • 1Department of Oncology, Albert Einstein-Montefiore Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA. cstein@montefiore.org

Seminars in Oncology
|December 13, 2005
PubMed
Summary

Antisense oligonucleotides, including G3139 targeting bcl-2 mRNA, show potential as cancer treatments. Further research is needed to address complexities in their clinical application for advanced melanoma, myeloma, and chronic lymphocytic leukemia.

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<i>REPLY</i>.

AJNR. American journal of neuroradiology·2018

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Antisense oligonucleotides (ASOs) are being investigated as cancer therapeutics.
  • G3139, a phosphorothioate oligomer targeting bcl-2 mRNA, has undergone Phase III clinical trials for advanced cancers.
  • Previous trials yielded mixed results, necessitating a deeper understanding of ASO mechanisms.

Purpose of the Study:

  • To review the mechanism of antisense effect, including cellular uptake and RNase H activity.
  • To describe the properties of phosphorothioate oligonucleotides used in clinical trials.
  • To discuss pharmacokinetic data from earlier phase I and II trials.

Main Methods:

  • Review of existing clinical trial data (Phase I, II, and III).
  • Analysis of the mechanism of action for antisense oligonucleotides.

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  • Examination of physicochemical properties of phosphorothioate oligonucleotides.

    • Main Results:

    • Phase III trials of G3139 in advanced melanoma, myeloma, and chronic lymphocytic leukemia (CLL) have been completed.
    • The efficacy of antisense oligonucleotides is dependent on cellular internalization and RNase H activity.
    • Phosphorothioate oligonucleotides exhibit specific and nonspecific properties.

    Conclusions:

    • Antisense technology offers a conceptually simple approach to cancer treatment.
    • Practical application involves complex, mechanistically based challenges.
    • Further investigation is required to optimize antisense oligonucleotide therapy for various cancers.