The Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, The Clinical Research Institute at Rambam Healthcare Campus, Technion Integrated Cancer Center, Rappaport Institute of Medicine and Research, Technion, Israel Institute of Technology, Haifa, Israel.
The Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, The Clinical Research Institute at Rambam Healthcare Campus, Technion Integrated Cancer Center, Rappaport Institute of Medicine and Research, Technion, Israel Institute of Technology, Haifa, Israel.
Drug Resist Updat. 2019 Jul;45:1-12. doi: 10.1016/j.drup.2019.07.003. Epub 2019 Jul 23.
Exosomes are a class of extracellular vesicles ranging in size from 40 to 100 nm, which are secreted by both cancer cells and multiple stromal cells in the tumor microenvironment. Following their secretion, exosomes partake in endocrine, paracrine and autocrine signaling. Internalization of exosomes by tumor cells influences several cellular pathways which alter cancer cell physiology. Tumor-derived exosomes secreted by cancer or stromal cells can also confer anticancer drug-resistant traits upon cancer cells. These exosomes promote chemoresistance by transferring their cargo which includes nucleic acids, proteins, and metabolites to cancer cells or act as a decoy for immunotherapeutic targets. Depletion of exosomes can reverse some of the detrimental effects on tumor metabolism and restore drug sensitivity to chemotherapeutic treatment. Herein we discuss various approaches that have been developed to deplete exosomes for therapeutic purposes. The natural composition, low immunogenicity and cytotoxicity of exosomes, along with their ability to specifically target tumor cells, render them an appealing platform for drug delivery. The ability of exosomes to mediate autocrine and paracrine signaling in target cells, along with their natural structure and low immunogenicity render them an attractive vehicle for the delivery of anticancer drugs to tumors.
外泌体是一类细胞外囊泡，大小在 40 至 100nm 之间，由肿瘤微环境中的癌细胞和多种基质细胞分泌。外泌体分泌后，参与内分泌、旁分泌和自分泌信号转导。肿瘤细胞对内泌体的内化会影响多种细胞途径，从而改变癌细胞的生理特性。肿瘤细胞分泌的肿瘤来源的外泌体，或由癌细胞或基质细胞分泌的外泌体，也可以赋予癌细胞抗癌药物耐药性特征。这些外泌体通过将其货物（包括核酸、蛋白质和代谢物）转移到癌细胞中，或作为免疫治疗靶点的诱饵，促进化学耐药性。耗尽外泌体可以逆转一些对肿瘤代谢的不利影响，并恢复对化疗的药物敏感性。本文讨论了为治疗目的而开发的各种耗尽外泌体的方法。外泌体的天然组成、低免疫原性和细胞毒性，以及它们特异性靶向肿瘤细胞的能力，使它们成为一种有吸引力的药物递送平台。外泌体在靶细胞中介导自分泌和旁分泌信号的能力，以及它们的天然结构和低免疫原性，使它们成为向肿瘤输送抗癌药物的有吸引力的载体。
