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The role of extracellular vesicles in the transfer of drug resistance competences to cancer cells
Drug Resistance Updates ( IF 15.8 ) Pub Date : 2022-04-05 , DOI: 10.1016/j.drup.2022.100833
Cristina P R Xavier 1 , Dimas Carolina Belisario 2 , Rita Rebelo 1 , Yehuda G Assaraf 3 , Elisa Giovannetti 4 , Joanna Kopecka 2 , M Helena Vasconcelos 5
Affiliation  

Drug resistance remains a major hurdle to successful cancer treatment, being accountable for approximately 90% of cancer-related deaths. In the past years, increasing attention has been given to the role of extracellular vesicles (EVs) in the horizontal transfer of drug resistance in cancer. Indeed, many studies have described the dissemination of therapy resistance traits mediated by EVs, which may be transferred from drug resistant tumor cells to their drug sensitive counterparts. Importantly, different key players of drug resistance have been identified in the cargo of those EVs, such as drug efflux pumps, oncoproteins, antiapoptotic proteins, or microRNAs, among others. Interestingly, the EVs-mediated crosstalk between cells from the tumor microenvironment (TME) and tumor cells has emerged as another important mechanism that leads to cancer cells drug resistance. Recently, the cargo of the TME-derived EVs responsible for the transfer of drug resistance traits has also become a focus of attention. In addition, the possible mechanisms involved in drug sequestration by EVs, likely to contribute to cancer drug resistance, are also described and discussed herein. Despite the latest scientific advances in the field of EVs, this is still a challenging area of research, particularly in the clinical setting. Therefore, further investigation is needed to assess the relevance of EVs to the failure of cancer patients to drug treatment, to identify biomarkers of drug resistance in the EV’s cargo, and to develop effective therapeutic strategies to surmount drug resistance. This up-to-date review summarizes relevant literature on the role of EVs in the transfer of drug resistance competences to cancer cells, and the relevance of tumor cells and of TME cells in this process. Finally, this knowledge is integrated with a discussion of possible future clinical applications of EVs as biomarkers of drug resistance.



中文翻译:

细胞外囊泡在将耐药能力转移到癌细胞中的作用

耐药性仍然是成功治疗癌症的主要障碍,约占癌症相关死亡的 90%。在过去的几年里,细胞外囊泡(EVs)在癌症耐药性水平转移中的作用越来越受到关注。事实上,许多研究已经描述了由 EV 介导的治疗抗性特征的传播,这些特征可能从耐药肿瘤细胞转移到其药物敏感对应物。重要的是,已经在这些 EV 的货物中发现了不同的耐药性关键因素,例如药物外排泵、癌蛋白、抗凋亡蛋白或 microRNA 等。有趣的是,EVs介导的肿瘤微环境(TME)细胞与肿瘤细胞之间的串扰已成为导致癌细胞耐药的另一个重要机制。最近,负责转移耐药性状的 TME 衍生 EV 的货物也成为关注的焦点。此外,本文还描述和讨论了 EV 药物隔离可能导致癌症耐药性的可能机制。尽管电动汽车领域取得了最新的科学进展,但这仍然是一个具有挑战性的研究领域,尤其是在临床环境中。因此,需要进一步调查以评估 EV 与癌症患者药物治疗失败的相关性,以确定 EV 货物中耐药性的生物标志物,并制定有效的治疗策略以克服耐药性。这篇最新综述总结了有关 EV 在将耐药性能力转移到癌细胞中的作用以及肿瘤细胞和 TME 细胞在此过程中的相关性的相关文献。最后,将这些知识与对 EV 作为耐药性生物标志物的未来临床应用的讨论相结合。

更新日期:2022-04-05
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