Deciphering the contributions of extracellular vesicles to cancer metastasis: Mechanisms and therapeutic implications.

Extracellular vesicles(EVs) including exosomes, microvesicles, and apoptotic bodies, have garnered significant attention for their pivotal roles in cancer metastasis. These nanometer-sized vesicles, secreted by both tumor and non-tumor cells, mediate intercellular communication by transferring bioactive molecules such as proteins, lipids, RNAs and metabolites. In the context of cancer, EVs facilitate metastasis by promoting tumor cell migration, invasion, angiogenesis, and immune evasion. Furthermore, EVs play a critical role in preparing distant organs for metastasis by shaping the Premetastatic Niche (PMN), thus creating a conductive microenvironment for tumor cell colonization. This review provides an in-depth exploration of the molecular mechanisms through which EVs influence cancer progression, with a focus on their roles in metastatic dissemination. Additionally, the emerging therapeutic strategies targeting EVs to inhibit metastasis, such as blocking EV biogenesis and secretion, disrupting EV-receptor interactions, and using EVs as delivery vehicles for targeted therapies are discussed. Moreover, exosome-based immunotherapies, which aim to enhance anti-tumor immunity, are also highlighted. While these therapeutic approaches hold great promise, challenges remain in efficiently targeting and modulating EV functions for clinical applications. Other subtypes of EVs such as Mitovesicles, Migrasomes can be further studied to explore their significant role at different stages of cancer. Improvement in cargo profiling of EVs mainly the proteins and miRNAs could be a novel noninvasive biomarker for detection of cancer. This article offers a comprehensive overview of the multifaceted roles of EVs in cancer metastasis and the potential of EV-based therapies, laying the foundation for future cancer treatment strategies.