title: Current development of targeted oligonucleotide-based cancer therapies: Perspective on HER2-positive breast cancer treatment.
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.
authors.affiliation: 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.
authors.forename: Worapol
authors.initials: W
authors.lastname: Ngamcherdtrakul
authors.affiliation: 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.
authors.forename: David J
authors.initials: DJ
authors.lastname: Castro
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
authors.forename: Shenda
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
authors.forename: Jingga
authors.initials: J
authors.lastname: Morry
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
authors.forename: Moataz
authors.initials: M
authors.lastname: Reda
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA. Electronic address: grayjo@ohsu.edu.
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.affiliation: 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. Electronic address: yantasee@ohsu.edu.
authors.forename: Wassana
authors.initials: W
authors.lastname: Yantasee
mesh_terms: D061605:Administration, Intravenous / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D053758:Nanoparticles; D009841:Oligonucleotides / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D000067492:RNAi Therapeutics / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D009841:Oligonucleotides; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast cancer; Nanoparticle; Oligonucleotide; Targeted delivery; Targeted therapy; siRNA