Ngamcherdtrakul Worapol, Castro David J, Gu Shenda, Morry Jingga, Reda Moataz, Gray Joe W, Yantasee Wassana
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.
Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR 97239, USA.
Cancer Treat Rev. 2016 Apr;45:19-29. doi: 10.1016/j.ctrv.2016.02.005. Epub 2016 Feb 22.
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.
本综述讨论了各种类型的非编码寡核苷酸，它们作为小分子抑制剂和单克隆抗体之外的靶向癌症治疗新选择，已引起广泛关注。这些寡核苷酸可以靶向癌症的任何特征，不再局限于所谓的“可成药”靶点。因此，任何在癌症进展或耐药中起关键作用的已鉴定基因都可以用寡核苷酸进行靶向。其中，小干扰RNA（siRNA）由于RNA干扰机制强大且成熟，常用于基因沉默。尽管具有诸多优势，但siRNA的临床转化因缺乏有效的递送平台而受阻。本综述提供了用于全身siRNA递送的纳米颗粒开发的一般标准和考量因素。讨论了用于siRNA递送的不同类别的纳米颗粒候选物，并综述了全身癌症治疗临床试验的进展。最后，本综述以人表皮生长因子受体2（HER2）阳性乳腺癌为例，说明其可从siRNA技术中显著获益。还讨论了基于siRNA的疗法如何克服癌症对此类疗法的耐药性。
