Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Curr Pharm Des. 2023;29(34):2692-2701. doi: 10.2174/0113816128270476231023052228.
Ovarian cancer (OC) is one of the most common malignancies in women and is associated with poor outcomes. The treatment for OC is often associated with resistance to therapies and hence this has stimulated the search for alternative therapeutic approaches, including RNA-based therapeutics. However, this approach has some challenges that include RNA degradation. To solve this critical issue, some novel delivery systems have been proposed. In current years, there has been growing interest in the improvement of RNAbased therapeutics as a promising approach to target ovarian cancer and improve patient outcomes. This paper provides a practical insight into the use of RNA-based therapeutics in ovarian cancers, highlighting their potential benefits, challenges, and current research progress. RNA-based therapeutics offer a novel and targeted approach to treat ovarian cancer by exploiting the unique characteristics of RNA molecules. By targeting key oncogenes or genes responsible for drug resistance, siRNAs can effectively inhibit tumor growth and sensitize cancer cells to conventional therapies. Furthermore, messenger RNA (mRNA) vaccines have emerged as a revolutionary tool in cancer immunotherapy. MRNA vaccines can be designed to encode tumor-specific antigens, stimulating the immune system to distinguish and eliminate ovarian cancer cells. A nano-based delivery platform improves the release of loaded RNAs to the target location and reduces the off-target effects. Additionally, off-target effects and immune responses triggered by RNA molecules necessitate careful design and optimization of these therapeutics. Several preclinical and clinical researches have shown promising results in the field of RNA-based therapeutics for ovarian cancer. In a preclinical study, siRNA-mediated silencing of the poly (ADP-ribose) polymerase 1 (PARP1) gene, involved in DNA repair, sensitized ovarian cancer cells to PARP inhibitors, leading to enhanced therapeutic efficacy. In clinical trials, mRNA-based vaccines targeting tumor-associated antigens have demonstrated safety and efficacy in stimulating immune responses in ovarian cancer patients. In aggregate, RNA-based therapeutics represent a promising avenue for the therapy of ovarian cancers. The ability to specifically target oncogenes or stimulate immune responses against tumor cells holds great potential for improving patient outcomes. However, further research is needed to address challenges related to delivery, permanence, and off-target effects. Clinical trials assessing the care and effectiveness of RNAbased therapeutics in larger patient cohorts are warranted. With continued advancements in the field, RNAbased therapeutics have the potential to develop the management of ovarian cancer and provide new hope for patients.
卵巢癌 (OC) 是女性最常见的恶性肿瘤之一,预后较差。OC 的治疗常常与对治疗的耐药性相关,因此这刺激了对替代治疗方法的探索,包括基于 RNA 的治疗方法。然而,这种方法存在一些挑战,包括 RNA 降解。为了解决这个关键问题,已经提出了一些新的递送系统。近年来,人们对 RNA 为基础的治疗方法作为一种有前途的靶向卵巢癌的方法越来越感兴趣,以改善患者的预后。本文提供了一个实用的视角,探讨了 RNA 为基础的治疗方法在卵巢癌中的应用,强调了它们的潜在益处、挑战和当前的研究进展。基于 RNA 的治疗方法通过利用 RNA 分子的独特特性,提供了一种新颖的靶向治疗卵巢癌的方法。通过靶向关键致癌基因或对耐药性负责的基因,siRNA 可以有效地抑制肿瘤生长,并使癌细胞对传统治疗方法敏感。此外,信使 RNA (mRNA) 疫苗已成为癌症免疫治疗的一项革命性工具。mRNA 疫苗可以设计为编码肿瘤特异性抗原,刺激免疫系统区分和消除卵巢癌细胞。基于纳米的递药平台提高了载药 RNA 向靶位的释放,减少了脱靶效应。此外,RNA 分子引发的脱靶效应和免疫反应需要对这些治疗方法进行仔细的设计和优化。几项临床前和临床研究表明,在卵巢癌的 RNA 为基础的治疗领域取得了有希望的结果。在一项临床前研究中,沉默多聚(ADP-核糖)聚合酶 1 (PARP1) 基因的 siRNA 治疗,PARP1 基因参与 DNA 修复,使卵巢癌细胞对 PARP 抑制剂敏感,从而增强了治疗效果。在临床试验中,靶向肿瘤相关抗原的 mRNA 疫苗在刺激卵巢癌患者的免疫反应方面显示出安全性和有效性。总之,基于 RNA 的治疗方法为卵巢癌的治疗提供了一个很有前途的途径。特异性靶向致癌基因或刺激针对肿瘤细胞的免疫反应有很大的潜力,可以改善患者的预后。然而,需要进一步的研究来解决与递送、持久性和脱靶效应相关的挑战。需要进行评估 RNA 为基础的治疗方法在更大的患者群体中的疗效和安全性的临床试验。随着该领域的不断发展,基于 RNA 的治疗方法有可能改善卵巢癌的治疗,并为患者带来新的希望。