Cheng Hao-Yang, Su Guang-Liang, Wu Yu-Xuan, Chen Gang, Yu Zi-Li
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
J Pharm Anal. 2024 Jul;14(7):100920. doi: 10.1016/j.jpha.2023.12.010. Epub 2023 Dec 16.
Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy. Prior research has illuminated reasons behind drug resistance, including increased drug efflux, alterations in drug targets, and abnormal activation of oncogenic pathways. However, there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment (TME). Recent studies on extracellular vesicles (EVs) have provided valuable insights. EVs are membrane-bound particles secreted by all cells, mediating cell-to-cell communication. They contain functional cargoes like DNA, RNA, lipids, proteins, and metabolites from mother cells, delivered to other cells. Notably, EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs. This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance, covering therapeutic approaches like chemotherapy, targeted therapy, immunotherapy and even radiotherapy. Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance. Additionally, targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance. We highlight the importance of conducting in-depth mechanistic research on EVs, their cargoes, and functional approaches specifically focusing on EV subpopulations. These efforts will significantly advance the development of strategies to overcome drug resistance in anti-tumor therapy.
耐药性对实现抗肿瘤治疗的积极临床结果构成了重大挑战。先前的研究已经阐明了耐药性背后的原因，包括药物外排增加、药物靶点改变以及致癌途径的异常激活。然而，需要更深入地研究耐药细胞对亲代肿瘤细胞的影响以及肿瘤细胞与恶性肿瘤微环境（TME）之间复杂的相互作用。最近关于细胞外囊泡（EVs）的研究提供了有价值的见解。EVs是所有细胞分泌的膜结合颗粒，介导细胞间通讯。它们包含来自母细胞的功能性货物，如DNA、RNA、脂质、蛋白质和代谢物，并传递给其他细胞。值得注意的是，EVs越来越被认为是抗癌药物耐药性的调节因子。本综述旨在总结EV介导的抗肿瘤耐药机制，涵盖化疗、靶向治疗、免疫治疗甚至放疗等治疗方法。检测基于EV的生物标志物以预测耐药性有助于绕过抗肿瘤药物耐药性。此外，靶向抑制EV的生物发生和分泌成为对抗耐药性的一种有前景的方法。我们强调对EVs、其货物以及特别关注EV亚群的功能方法进行深入机制研究的重要性。这些努力将显著推动克服抗肿瘤治疗中耐药性策略的发展。
