Ciferri Maria Chiara, Tasso Roberta
Department of Experimental Medicine (DIMES), University of Genova, Genova 16132, Italy.
Dipartimento della Ricerca, IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy.
Extracell Vesicles Circ Nucl Acids. 2025 Feb 24;6(1):112-127. doi: 10.20517/evcna.2024.90. eCollection 2025.
The role of extracellular vesicles (EVs) in mediating chemoresistance has gained significant attention due to their ability to transfer bioactive molecules between drug-resistant and drug-sensitive cells. In particular, they have been demonstrated to play an active part in breast cancer chemoresistance by the horizontal transfer of genetic and protein material. This review highlights the role of EVs, particularly their miRNA cargo, in driving drug resistance in breast cancer. EVs derived from chemoresistant cells carry miRNAs and lncRNAs, which are known to modulate gene networks involved in cell proliferation and survival. These cargo molecules suppress apoptosis by targeting pro-apoptotic genes like PTEN and BIM, promote epithelial-mesenchymal transition (EMT) through the regulation of pathways such as TGF-β and Wnt/b-catenin, and contribute to tumor growth and resistance by enhancing angiogenesis and modulating the tumor microenvironment. Beyond RNA-mediated effects, EVs also transfer functional proteins, including P-glycoprotein and Hsp70, which impact cellular metabolism and survival pathways. Our findings underscore the significance of EVs in breast cancer chemoresistance, suggesting their potential involvement as possible prognostic factors to predict therapy response and as therapeutic targets in combination with usual therapy.
细胞外囊泡（EVs）在介导化疗耐药性方面的作用已受到广泛关注，因为它们能够在耐药细胞和药物敏感细胞之间传递生物活性分子。特别是，它们已被证明通过遗传和蛋白质物质的水平转移在乳腺癌化疗耐药中发挥积极作用。本综述强调了EVs，尤其是其携带的微小RNA（miRNA），在驱动乳腺癌耐药中的作用。源自耐药细胞的EVs携带miRNA和长链非编码RNA（lncRNA），已知这些分子可调节参与细胞增殖和存活的基因网络。这些携带的分子通过靶向PTEN和BIM等促凋亡基因来抑制细胞凋亡，通过调节TGF-β和Wnt/β-连环蛋白等信号通路促进上皮-间质转化（EMT），并通过增强血管生成和调节肿瘤微环境来促进肿瘤生长和耐药。除了RNA介导的作用外，EVs还传递功能蛋白，包括P-糖蛋白和热休克蛋白70（Hsp70），它们会影响细胞代谢和存活途径。我们的研究结果强调了EVs在乳腺癌化疗耐药中的重要性，表明它们可能作为预测治疗反应的潜在预后因素以及与常规治疗联合的治疗靶点。
