The role of small extracellular vesicles in ovarian cancer drug resistance: from bench clues to clinical implications

Ovarian cancer (OC) represents the most lethal gynecologic malignancy, characterized by complex molecular heterogeneity, immune evasion, and therapy resistance. Chemotherapy resistance constitutes a formidable challenge in the global management of ovarian cancer, severely compromising therapeutic efficacy and precipitating adverse clinical outcomes. The chemoresistance phenotype originates from intrinsic resistance traits or genetic alterations, encompassing gene mutations and chromosomal variations. Emerging evidence has elucidated the capacity of small extracellular vesicles (sEVs) within the tumor microenvironment (TME) to horizontally transfer functional proteins and non-coding RNAs, thereby conferring chemoresistance phenotypes to drug-sensitive cells. This review delineates the packaging, sorting, and phenotypic transfer mechanisms of sEVs in the TME, elucidating how these processes facilitate the dissemination of resistance phenotypes across ovarian cancer progression. We also reviewed the established sEV-based diagnostic and prognostic utilities, as well as sEV-mediated drug delivery platforms. The study provides novel insights into related mechanisms and technologies in drug resistance of ovarian cancer.