School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China.
Expert Opin Drug Discov. 2020 Jan;15(1):63-83. doi: 10.1080/17460441.2020.1690449. Epub 2019 Nov 19.
: MicroRNAs (miRNAs) are small endogenous non-coding RNAs that repress the expression of their target genes by reducing mRNA stability and/or inhibiting translation. miRNAs are known to be aberrantly regulated in cancers. Modulators of miRNA (mimics and antagonists) have emerged as novel therapeutic tools for cancer treatment.: This review summarizes the various strategies that have been applied to correct the dysregulated miRNA in cancer cells. The authors also discuss the recent advances in the technical development and preclinical/clinical evaluation of miRNA-based therapeutic agents.: Application of miRNA-based therapeutics for cancer treatment is appealing because they are able to modulate multiple dysregulated genes and/or signaling pathways in cancer cells. Major obstacles hindering their clinical development include drug delivery, off-target effects, efficacious dose determination, and safety. Tumor site-specific delivery of novel miRNA therapeutics may help to minimize off-target effects and toxicity. Combination of miRNA therapeutics with other anticancer treatment modalities could provide a synergistic effect, thus allowing the use of lower dose, minimizing off-target effects, and improving the overall safety profile in cancer patients. It is critical to identify individual miRNAs with cancer type-specific and context-specific regulation of oncogenes and tumor-suppressor genes in order to facilitate the precise use of miRNA anticancer therapeutics.
: 微小 RNA（miRNAs）是小型内源性非编码 RNA，通过降低 mRNA 稳定性和/或抑制翻译来抑制靶基因的表达。已知 miRNAs 在癌症中失调调控。miRNA 的调节剂（模拟物和拮抗剂）已成为癌症治疗的新型治疗工具。: 本文综述了应用于纠正癌细胞中失调 miRNA 的各种策略。作者还讨论了 miRNA 治疗剂的技术发展和临床前/临床评估的最新进展。: miRNA 治疗剂在癌症治疗中的应用具有吸引力，因为它们能够调节癌细胞中多个失调的基因和/或信号通路。阻碍其临床开发的主要障碍包括药物输送、脱靶效应、有效剂量确定和安全性。新型 miRNA 治疗剂的肿瘤部位特异性输送可能有助于最小化脱靶效应和毒性。miRNA 治疗剂与其他抗癌治疗方式的联合应用可能会产生协同作用，从而允许使用较低剂量，减少脱靶效应，并提高癌症患者的整体安全性。确定具有癌症类型特异性和与肿瘤抑制基因和癌基因特定调节的个体 miRNAs 对于促进 miRNA 抗癌治疗的精确应用至关重要。
