Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam U.M.C., VU. University Medical Center (VUMC), Amsterdam, the Netherlands.
Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam U.M.C., VU. University Medical Center (VUMC), Amsterdam, the Netherlands; General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Cytokine Growth Factor Rev. 2023 Oct;73:163-172. doi: 10.1016/j.cytogfr.2023.07.004. Epub 2023 Jul 29.
Chemoresistance constitute a major obstacle in cancer treatment, leading to limited options and decreased patient survival. Recent studies have revealed a novel mechanism of chemoresistance acquisition: the transfer of information via exosomes, small vesicles secreted by various cells. Exosomes play a crucial role in intercellular communication by carrying proteins, nucleic acids, and metabolites, influencing cancer cell behavior and response to treatment. One crucial mechanism of resistance is cancer metabolic reprogramming, which involves alterations in the cellular metabolic pathways to support the survival and proliferation of drug-resistant cancer cells. This metabolic reprogramming often includes increased glycolysis, providing cancer cells with the necessary energy and building blocks to evade the effects of chemotherapy. Notably, exosomes have been found to transport glycolytic enzymes, as identified in proteomic profiling, leading to the reprogramming of metabolic pathways, facilitating altered glucose metabolism and increased lactate production. As a result, they profoundly impact the tumor microenvironment, promoting tumor progression, survival, immune evasion, and drug resistance.Understanding the complexities of such exosome-mediated cell-to-cell communication might open new therapeutic avenues and facilitate biomarker development in managing cancers characterized by aggressive glycolytic features. Moreover, given the intricate nature of metabolic abnormalities combining future exosome-based-targeted therapies with existing treatments like chemotherapy, immunotherapy, and targeted therapies holds promise for achieving synergistic effects to overcome resistance and improve cancer treatment outcomes.
化学抗性是癌症治疗中的一个主要障碍，导致治疗选择有限，患者生存率降低。最近的研究揭示了化学抗性获得的一种新机制：通过外泌体（各种细胞分泌的小囊泡）进行信息传递。外泌体通过携带蛋白质、核酸和代谢物在细胞间通讯中发挥关键作用，影响癌细胞行为和对治疗的反应。一种关键的抗性机制是癌症代谢重编程，涉及细胞代谢途径的改变，以支持耐药癌细胞的存活和增殖。这种代谢重编程通常包括增加糖酵解，为耐药癌细胞提供逃避化疗影响所需的能量和构建块。值得注意的是，外泌体已被发现运输糖酵解酶，如蛋白质组学分析中所确定的，导致代谢途径的重新编程，促进葡萄糖代谢的改变和乳酸的产生增加。因此，它们深刻地影响肿瘤微环境，促进肿瘤进展、存活、免疫逃避和耐药性。
理解这种外泌体介导的细胞间通讯的复杂性可能为管理具有侵袭性糖酵解特征的癌症开辟新的治疗途径，并促进生物标志物的发展。此外，鉴于代谢异常的复杂性，将未来基于外泌体的靶向治疗与化疗、免疫疗法和靶向治疗等现有治疗方法相结合，有望产生协同作用，克服耐药性，改善癌症治疗效果。
