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叩开细胞之门:miRNA和siRNA在抗癌治疗中的策略方法

Knocking on Cells' Door: Strategic Approaches for miRNA and siRNA in Anticancer Therapy.

作者信息

Serra Massimo, Buccellini Alessia, Paolillo Mayra

机构信息

Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy.

出版信息

Int J Mol Sci. 2025 Sep 6;26(17):8703. doi: 10.3390/ijms26178703.

Abstract

Metastasis is the main cause of failure in anticancer therapies, and is frequently related to poor prognosis for patients. The true challenge in extending cancer patient life expectancy, eventually managing cancer as a chronic disease with periodic but controllable relapses, relies on the development of effective therapeutic strategies specifically targeting key mechanisms involved in the metastatic cascade. Traditional chemotherapy with alkylating agents, microtubule inhibitors, and antimetabolites has shown limited efficacy against metastatic cells, largely due to the emergence of chemoresistant populations that undergo epithelial-to-mesenchymal transition (EMT), promoting the colonization of distant organs and sustaining metastatic progression. This scenario has spurred significant efforts to identify small molecules and biologics capable of interfering with specific steps in the metastatic process. In this review, we provide an overview of recent advances involving small interfering RNAs (siRNAs) and microRNAs (miRNAs) in cancer therapy. Although most of these agents are still under investigation and have not yet been approved for clinical use, insights into their development stage offer valuable information to identify new targets in the ongoing fight against metastasis. Particular emphasis is placed on the role of chemical modifications applied to siRNAs, such as backbone, sugar, terminal, base, and conjugation changes, and how these factors influence their stability, immunogenicity, and targeting precision. By integrating these aspects into the discussion, this review provides a focused and up-to-date resource for researchers in medicinal chemistry, drug delivery, and pharmaceutical formulation, where molecular design plays a critical role in therapeutic success.

摘要

转移是抗癌治疗失败的主要原因,且常常与患者的不良预后相关。延长癌症患者预期寿命的真正挑战,最终是将癌症作为一种具有周期性但可控复发的慢性病来管理,这依赖于开发专门针对转移级联反应中关键机制的有效治疗策略。使用烷化剂、微管抑制剂和抗代谢物的传统化疗对转移细胞的疗效有限,这主要是由于出现了经历上皮-间质转化(EMT)的化疗耐药群体,促进了远处器官的定植并维持转移进展。这种情况促使人们大力努力去识别能够干扰转移过程中特定步骤的小分子和生物制剂。在本综述中,我们概述了小干扰RNA(siRNA)和微小RNA(miRNA)在癌症治疗中的最新进展。尽管这些药物大多仍在研究中,尚未被批准用于临床,但对其开发阶段的深入了解为在当前抗击转移的斗争中识别新靶点提供了有价值的信息。特别强调了应用于siRNA的化学修饰的作用,如主链、糖、末端、碱基和缀合变化,以及这些因素如何影响其稳定性、免疫原性和靶向精度。通过将这些方面纳入讨论,本综述为药物化学、药物递送和药物制剂领域的研究人员提供了一个重点突出且最新的资源,其中分子设计在治疗成功中起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffb9/12429660/da3196252958/ijms-26-08703-g001.jpg

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