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Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance.
Drug Resistance Updates ( IF 15.8 ) Pub Date : 2019-10-15 , DOI: 10.1016/j.drup.2019.100647
M Helena Vasconcelos 1 , Hugo R Caires 2 , Artūrs Ābols 3 , Cristina P R Xavier 2 , Aija Linē 4
Affiliation  

Cancer-derived extracellular vesicles (EVs) have been detected in the bloodstream and other biofluids of cancer patients. They carry various tumor-derived molecules such as mutated DNA and RNA fragments, oncoproteins as well as miRNA and protein signatures associated with various phenotypes. The molecular cargo of EVs partially reflects the intracellular status of their cellular origin, however various sorting mechanisms lead to the enrichment or depletion of EVs in specific nucleic acids, proteins or lipids. It is becoming increasingly clear that cancer-derived EVs act in a paracrine and systemic manner to promote cancer progression by transferring aggressive phenotypic traits and drug-resistant phenotypes to other cancer cells, modulating the anti-tumor immune response, as well as contributing to remodeling the tumor microenvironment and formation of pre-metastatic niches. These findings have raised the idea that cancer-derived EVs may serve as analytes in liquid biopsies for real-time monitoring of tumor burden and drug resistance. In this review, we have summarized recent longitudinal clinical studies describing promising EV-associated biomarkers for cancer progression and tracking cancer evolution as well as pre-clinical and clinical evidence on the relevance of EVs for monitoring the emergence or progression of drug resistance. Furthermore, we outlined the state-of-the-art in the development and commercialization of EV-based biomarkers and discussed the scientific and technological challenges that need to be met in order to translate EV research into clinically applicable tools for precision medicine.



中文翻译:

细胞外囊泡是液体活检中用于监测癌症进展和耐药性的新型生物标志物来源。

在癌症患者的血液和其他生物流体中已检测到癌症来源的细胞外囊泡(EVs)。它们携带各种肿瘤来源的分子,例如突变的DNA和RNA片段,癌蛋白以及与各种表型相关的miRNA和蛋白标记。电动汽车的分子货物部分反映了其细胞起源的细胞内状态,但是各种分类机制导致电动汽车在特定核酸,蛋白质或脂质中的富集或耗竭。越来越清楚的是,源自癌症的EV通过将侵略性表型特征和耐药性表型转移至其他癌细胞,调节抗肿瘤免疫反应,以旁分泌和全身性方式来促进癌症进展。以及有助于重塑肿瘤微环境和转移前小生境的形成。这些发现提出了一种想法,即癌症衍生的电动汽车可以用作液体活检中的分析物,以实时监测肿瘤负荷和耐药性。在这篇综述中,我们总结了近期的纵向临床研究,这些研究描述了有希望的与EV相关的生物标记物,用于癌症进展并跟踪癌症的进展,以及有关EV在监测耐药性出现或进展中的相关性的临床前和临床证据。此外,我们概述了基于EV的生物标记物开发和商业化的最新技术,并讨论了将EV研究转化为精准医学的临床适用工具所需要解决的科学和技术挑战。

更新日期:2019-10-15
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