Extracellular vesicles in prostate cancer: current understanding and future perspectives

Exosomes are nanoscale, lipid bilayer extracellular vesicles (EVs) actively secreted by cells under both physiological and pathological conditions. As key mediators of intercellular communication, exosomes carry a diverse array of molecular cargo, including nucleic acids, proteins, lipids, and metabolites, which can influence the function of recipient cells. Based on evidence from 2016-2025 across PubMed, Embase, the Cochrane Library, and clinicaltrials.org, this review consolidates current understanding of exosome biology in prostate cancer (PCa). We discuss exosome biogenesis, molecular cargo composition, and their functional roles in tumor progression, angiogenesis, immune evasion, metastasis, and therapy resistance of PCa. We emphasize the biomarker potential of exosomes, which can overcome the limitations of PSA, such as poor specificity and overdiagnosis. Unlike free-circulating molecules, the exosomal lipid bilayer protects its cargo from enzymatic degradation, thereby stabilizing prostate-specific markers such as AR-V7, PCA3, ERG mRNAs, PSMA protein, and other microRNAs. Furthermore, we highlight that exosomes derived from urine and prostatic secretions could serve as promising biomarkers for early diagnosis, prognosis, and monitoring therapeutic response (via longitudinal sampling) due to the prostate's anatomical proximity to these fluids. Despite this wealth of information, significant challenges in standardized isolation techniques and clinical application due to tumor heterogeneity remain. This review also aims to bridge existing gaps and provide future prospectives toward hybrid isolation techniques, cell-specific exosome profiling, and artificial intelligence (AI)-driven multi-omics data integration to leverage exosome biology and address PCa-specific biomarkers and heterogeneity, thereby improving patient outcomes.