Exosomal proteins in prostate cancer progression: from mechanisms to diagnostic and therapeutic applications

Prostate cancer (PCa) remains a leading cause of cancer death in men, and the limitations of prostate-specific antigen (PSA) testing continue to delay diagnosis and confound risk stratification. Exosomes, small extracellular vesicles that can be recovered non-invasively from blood and urine, provide a window onto tumour biology, and the proteins they carry are the most readily measurable of their cargoes for clinical assay development. This review summarises how exosomal proteins sustain four programmes that jointly drive PCa progression: Wnt/β-catenin-dependent metastasis, angiogenesis, immune evasion and the suppression of ferroptosis, the iron-dependent, lipid-peroxidation-driven cell death to which treatment-resistant PCa is vulnerable. Each protein is considered together with its cell of origin, carcinoma cells, cancer-associated fibroblasts or tumour-associated macrophages, because the same molecule can act differently depending on the cell that released it. Key examples include GIPC2, which engages the Wnt co-receptor Fzd7 to activate β-catenin signalling; PGAM1, which binds γ-actin in endothelial cells to promote angiogenesis; exosomal PD-1 and PD-L1, which respectively activate myeloid-derived suppressor cells and suppress CD8 + T cells; and FTH1P8 together with CAF-derived miR-432–5p, which blunt ferroptosis and sustain docetaxel and antiandrogen resistance. The review also covers the diagnostic value of urinary exosomal proteins such as PSMA and PSA, the difference between these protein markers and the RNA-based ExoDx EPI test, and the emerging advances, from GMP-compliant manufacturing and single-vesicle quantification to regulatory guidance, that are beginning to overcome the barriers of isolation heterogeneity, scalability, immunogenicity and regulation.