Small Extracellular Vesicles: Unraveling Their Roles in Ovarian Cancer Progression and Tapping Into Clinical Application Potential

Among gynecologic malignancies, ovarian cancer (OC) stands out as a highly aggressive disease with the highest mortality rate and the poorest prognosis. At the beginning stage, it demonstrates high sensitivity to platinum-based chemotherapy. Nevertheless, most patients will encounter recurrence following the initial surgery and chemotherapy. Small extracellular vesicles (sEVs), characterized by a "cup-shaped" morphology and with a diameter of 40 to 160 nm, encompass diverse biologically active substances including nucleic acids (such as DNA, mRNA, microRNA (miRNA), and other non-coding RNAs (ncRNAs)), as well as oncogenic proteins, lipids, and metabolites, which play a crucial role as mediators of intercellular communication. Increasing evidence shows that sEVs promote various cancers' progression (including OC) via transporting molecular cargoes to target cells or organs. It is worth mentioning that existing literature often focuses on sEVs from a single cell type and lacks a comprehensive review of multiple cell sources. In this review, we summarize the biological functions of sEVs derived from different cell types in OC, including regulating cell proliferation, promoting metastasis, mediating drug resistance, inducing angiogenesis, facilitating immune escape, and maintaining stemness. Meanwhile, we focus on exploring the clinical value of sEVs as biomarkers for the diagnosis and prognosis of OC, as well as their application potential in translational medicine fields related to cancer vaccine development, targeted drug delivery, and precision tumor-targeted therapy. Additionally, we analyze the major challenges currently faced in sEV-based OC treatment research and propose potential strategies to overcome these limitations.