维奈克拉作为首个B细胞淋巴瘤2(B-cell lymphoma 2, BCL-2)选择性抑制剂, 在多种血液系统肿瘤的治疗中展现出显著疗效,但其在临床应用过程中逐渐暴露出的耐药问题, 严重限制了疗效的持久性并影响患者预后。近年来, 大量研究表明, 外泌体作为细胞间通讯的重要介质, 在维奈克拉耐药形成中发挥关键作用,其可通过携带蛋白质、miRNA 和lncRNA 等活性成分, 调控凋亡信号通路、介导能量代谢重编程、促进药物外排及诱导肿瘤微环境重塑, 促进肿瘤细胞存活,并逃避维奈克拉诱导的细胞凋亡。本文系统总结了外泌体在维奈克拉耐药机制中的最新研究进展, 旨在为阐明维奈克拉耐药形成的网络调控机制、恢复药物敏感性、开发外泌体靶向干预策略提供理论依据与研究方向。

Venetoclax, the first selective inhibitor of B-cell lymphoma 2 (BCL-2), has demonstrated remarkable therapeutic efficacy in the treatment of various hematologic malignancies.However, the emergence of drug resistance during clinical application has limited the durability of its efficacy and adversely affected patient prognosis. In recent years, accumulating evidence has revealed that exosomes, as critical mediators of intercellular communication, play a pivotal role in the development of venetoclax resistance. Exosomes can transport bioactive molecules, including proteins,microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), thereby regulating apoptotic signaling pathways, mediating metabolic reprogramming, promoting drug efflux, and inducing remodeling of the tumor microenvironment. Through these mechanisms, exosomes enhance tumor cell survival and allow evasion of venetoclax-induced apoptosis. This review systematically summarizes the latest advances in exosome-mediated mechanisms of venetoclax resistance, aiming to elucidate the network-based regulatory mechanisms underlying resistance development, help reverse drug resistance and restore drug sensitivity, and provide theoretical foundations and research directions for the development of exosome-targeted therapeutic strategies.