Mirón-Barroso Sofía, Correia Joana S, Frampton Adam E, Lythgoe Mark P, Clark James, Tookman Laura, Ottaviani Silvia, Castellano Leandro, Porter Alexandra E, Georgiou Theoni K, Krell Jonathan
Department of Surgery and Cancer, Imperial College, London W12 0HS, UK.
Department of Materials, Imperial College London, London SW7 2AZ, UK.
Noncoding RNA. 2022 Aug 2;8(4):58. doi: 10.3390/ncrna8040058.
As research uncovers the underpinnings of cancer biology, new targeted therapies have been developed. Many of these therapies are small molecules, such as kinase inhibitors, that target specific proteins; however, only 1% of the genome encodes for proteins and only a subset of these proteins has 'druggable' active binding sites. In recent decades, RNA therapeutics have gained popularity due to their ability to affect targets that small molecules cannot. Additionally, they can be manufactured more rapidly and cost-effectively than small molecules or recombinant proteins. RNA therapeutics can be synthesised chemically and altered quickly, which can enable a more personalised approach to cancer treatment. Even though a wide range of RNA therapeutics are being developed for various indications in the oncology setting, none has reached the clinic to date. One of the main reasons for this is attributed to the lack of safe and effective delivery systems for this type of therapeutic. This review focuses on current strategies to overcome these challenges and enable the clinical utility of these novel therapeutic agents in the cancer clinic.
随着研究揭示癌症生物学的基础,新的靶向疗法得以开发。其中许多疗法是小分子,如激酶抑制剂,可靶向特定蛋白质;然而,只有1%的基因组编码蛋白质,且这些蛋白质中只有一部分具有“可成药”的活性结合位点。近几十年来,RNA疗法因其能够作用于小分子无法作用的靶点而受到青睐。此外,与小分子或重组蛋白相比,它们的生产速度更快且成本效益更高。RNA疗法可以通过化学合成并快速改变,这能够实现更个性化的癌症治疗方法。尽管目前正在为肿瘤学领域的各种适应症开发多种RNA疗法,但迄今为止尚无一种进入临床应用。造成这种情况的主要原因之一是缺乏针对这类疗法的安全有效的递送系统。本综述重点关注克服这些挑战并使这些新型治疗药物在癌症临床中发挥临床效用的当前策略。