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细胞外囊泡在癌症治疗中的应用。

Extracellular vesicles in cancer therapy.

机构信息

Department of Pathology, University of California, San Diego, CA 92093, USA.

出版信息

Semin Cancer Biol. 2022 Nov;86(Pt 2):296-309. doi: 10.1016/j.semcancer.2022.06.001. Epub 2022 Jun 8.

Abstract

Extracellular vesicles (EVs), including a variety of membrane-enclosed nanosized particles carrying cell-derived cargo, mediate a major type of intercellular communication in physiological and pathological processes. Both cancer and non-cancer cells secrete EVs, which can travel to and influence various types of cells at the primary tumor site as well as in distant organs. Tumor-derived EVs contribute to cancer cell plasticity and resistance to therapy, adaptation of tumor microenvironment, local and systemic vascular remodeling, immunomodulation, and establishment of pre-metastatic niches. Therefore, targeting the production, uptake, and function of tumor-derived EVs has emerged as a new strategy for stand-alone or combinational therapy of cancer. On the other hand, as EV cargo partially reflects the genetic makeup and phenotypic properties of the secreting cell, EV-based biomarkers that can be detected in biofluids are being developed for cancer diagnosis and for predicting and monitoring tumor response to therapy. Meanwhile, EVs from presumably safe sources are being developed as delivery vehicles for anticancer therapeutic agents and as anticancer vaccines. Numerous reviews have discussed the biogenesis and characteristics of EVs and their functions in cancer. Here, I highlight recent advancements in translation of EV research outcome towards improved care of cancer, including developments of non-invasive EV-based biomarkers and therapeutic agents targeting tumor-derived EVs as well as engineering of therapeutic EVs.

摘要

细胞外囊泡(EVs),包括各种携带细胞来源货物的膜封闭纳米颗粒,在生理和病理过程中介导主要类型的细胞间通讯。癌细胞和非癌细胞都分泌 EVs,它们可以转移到原发性肿瘤部位和远处器官的各种类型的细胞,并影响这些细胞。肿瘤衍生的 EVs 有助于癌细胞的可塑性和对治疗的耐药性、肿瘤微环境的适应、局部和全身血管重塑、免疫调节以及前转移龛的建立。因此,针对肿瘤衍生 EV 的产生、摄取和功能已成为癌症单独或联合治疗的新策略。另一方面,由于 EV 货物部分反映了分泌细胞的遗传构成和表型特性,因此正在开发可在生物流体中检测到的基于 EV 的生物标志物,用于癌症诊断以及预测和监测肿瘤对治疗的反应。同时,来自假定安全来源的 EV 被开发为抗癌治疗剂的递送载体和抗癌疫苗。许多综述讨论了 EV 的生物发生和特征及其在癌症中的功能。在这里,我强调了 EV 研究成果向改善癌症治疗的转化方面的最新进展,包括开发非侵入性的基于 EV 的生物标志物和针对肿瘤衍生 EV 的治疗剂,以及治疗性 EV 的工程。

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