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Current development of targeted oligonucleotide-based cancer therapies: Perspective on HER2-positive breast cancer treatment

  • Worapol Ngamcherdtrakul
    Affiliations
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA

    PDX Pharmaceuticals, LLC, 3303 SW Bond Ave, Portland, OR 97239, USA
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  • David J. Castro
    Affiliations
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA

    PDX Pharmaceuticals, LLC, 3303 SW Bond Ave, Portland, OR 97239, USA
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  • Shenda Gu
    Affiliations
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA
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  • Jingga Morry
    Affiliations
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA
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  • Moataz Reda
    Affiliations
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA
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  • Joe W. Gray
    Correspondence
    Corresponding author at: 3303 SW Bond Ave, Portland, OR 97239, USA. Tel.: +1 503 418 9306; fax: +1 503 418 9311.
    Affiliations
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA
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  • Wassana Yantasee
    Correspondence
    Corresponding author at: 3303 SW Bond Ave, Portland, OR 97239, USA. Tel.: +1 503 418 9306; fax: +1 503 418 9311.
    Affiliations
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA

    PDX Pharmaceuticals, LLC, 3303 SW Bond Ave, Portland, OR 97239, USA
    Search for articles by this author
Published:February 21, 2016DOI:https://doi.org/10.1016/j.ctrv.2016.02.005

      Highlights

      • Oligonucleotides as alternative candidates for targeted therapies.
      • siRNAs open doors to hitting ‘undruggable’ targets.
      • Translation of siRNAs to clinics is dependent on delivery platform.
      • Nanoparticles have been widely studied for siRNA delivery.
      • siRNAs have great potential in drug-resistant HER2-positive breast cancer.

      Abstract

      This Review discusses the various types of non-coding oligonucleotides, which have garnered extensive interest as new alternatives for targeted cancer therapies over small molecule inhibitors and monoclonal antibodies. These oligonucleotides can target any hallmark of cancer, no longer limited to so-called “druggable” targets. Thus, any identified gene that plays a key role in cancer progression or drug resistance can be exploited with oligonucleotides. Among them, small-interfering RNAs (siRNAs) are frequently utilized for gene silencing due to the robust and well established mechanism of RNA interference. Despite promising advantages, clinical translation of siRNAs is hindered by the lack of effective delivery platforms. This Review provides general criteria and consideration of nanoparticle development for systemic siRNA delivery. Different classes of nanoparticle candidates for siRNA delivery are discussed, and the progress in clinical trials for systemic cancer treatment is reviewed. Lastly, this Review presents HER2 (human epidermal growth factor receptor type 2)-positive breast cancer as one example that could benefit significantly from siRNA technology. How siRNA-based therapeutics can overcome cancer resistance to such therapies is discussed.

      Graphical abstract

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