Sonwane Sandip, Telrandhe Umesh, Chambhare Nikhita, Vaidya Sunita
Datta Meghe College of Pharmacy, DMIHER (DU), Sawangi, Wardha, Wardha, India.
J Egypt Natl Canc Inst. 2025 May 1;37(1):30. doi: 10.1186/s43046-025-00289-9.
Extracellular vesicles (EVs) have emerged as key cell-to-cell communication mediators and play significant roles in both physiological and pathological processes. In EVs, exosomes represent a distinct subpopulation of EVs that have been found to be involved in cancer initiation and therapeutic resistance. Exosomes transfer a diverse spectrum of molecular cargos that have significant effects on the tumor microenvironment (TME), thereby enabling cancer initiation, metastasis, and therapeutic resistance. Exosomes have recently been of interest in cancer therapy due to their role as important mediators of treatment resistance. The exosomal molecular content-proteins, miRNAs, and lncRNAs-allows exosomes to perform functions including drug efflux and detoxification, cell death pathway modulation, induction of epithelial-to-mesenchymal transition (EMT), and suppression of the immune system. In addition to facilitating immune and stromal cell interactions, exosomes cause extracellular matrix remodeling and induce tumor heterogeneity, making it more difficult to respond to therapy. This review covers intricate roles of exosomes in cancer therapy resistance with regard to their biogenesis, molecular content, and functional impact in the TME. Along with this, we also discuss new therapeutic strategies to overcome exosome-mediated resistance including utilizing exosome inhibitors, designed exosome therapy, and combination with conventional therapies. While exosomes hold promise in prediction and diagnosis through their biomarker function, their heterogeneous origins and cryptic functions make it difficult to target interventions. This review emphasizes that research on exosome-mediated pathways is urgently required to develop new therapeutic strategies that can improve cancer treatment outcomes.
细胞外囊泡（EVs）已成为关键的细胞间通讯介质，在生理和病理过程中均发挥着重要作用。在细胞外囊泡中，外泌体是一种独特的亚群，已发现其与癌症的发生和治疗耐药性有关。外泌体可转运多种分子货物，这些货物对肿瘤微环境（TME）具有显著影响，从而促进癌症的发生、转移和治疗耐药性。由于外泌体作为治疗耐药性的重要介质，最近在癌症治疗中受到关注。外泌体的分子成分——蛋白质、微小RNA（miRNAs）和长链非编码RNA（lncRNAs）——使外泌体能够执行包括药物外排和解毒、细胞死亡途径调节、上皮-间质转化（EMT）诱导以及免疫系统抑制等功能。除了促进免疫细胞和基质细胞相互作用外，外泌体还会导致细胞外基质重塑并诱导肿瘤异质性，使得对治疗的反应更加困难。本综述涵盖了外泌体在癌症治疗耐药性方面的复杂作用，涉及其生物发生、分子成分以及在肿瘤微环境中的功能影响。与此同时，我们还讨论了克服外泌体介导的耐药性的新治疗策略，包括利用外泌体抑制剂、设计外泌体疗法以及与传统疗法联合使用。虽然外泌体通过其生物标志物功能在预测和诊断方面具有潜力，但其异质性起源和隐秘功能使得难以进行靶向干预。本综述强调，迫切需要对外泌体介导的途径进行研究，以开发能够改善癌症治疗效果的新治疗策略。
