Extracellular vesicles-mediated metabolic reprogramming in prostate cancer progression and tumor microenvironment remodeling

Metabolic reprogramming in prostate cancer (PCa) is a staged reorganization of the specialized citrate-producing metabolism of normal prostate epithelium. Malignant transformation reverses the zinc–citrate axis and restores mitochondrial oxidation, followed by androgen receptor-linked lipid remodeling, nutrient flexibility, and organelle and lineage plasticity. Extracellular vesicles (EVs), particularly exosomes/small extracellular vesicles (sEVs), can externalize aspects of these states by transferring proteins, regulatory RNAs, metabolites, and lipids. Across tumor, stromal, immune, vascular, and metastatic compartments, EV-mediated transfer may redistribute nutrients and reshape bioenergetic, redox, and lipid programs in recipient cells. These processes link intercellular metabolic adaptation to proliferation, angiogenesis, metastasis, therapy resistance, immunosuppression, and tumor microenvironment (TME) remodeling. This review integrates PCa-specific metabolic architecture with EV/sEV cargo selection, transfer, uptake, and recipient-cell responses, emphasizing how these processes generate biological and clinical consequences. Evidence for some proposed EV-metabolism axes remains indirect or emerging, and their interpretation requires evidence-matched claims. By placing EV/sEV signaling within broader intercellular communication networks, we outline implications for biomarkers, disease monitoring, and therapeutic development. EV/sEV-mediated metabolic communication thus offers a biologically grounded view of PCa progression and microenvironmental adaptation.