Metabolic Messengers: Extracellular Vesicles as Central Mediators of Metabolic Reprogramming in Renal Cell Cancer

Renal cell carcinoma (RCC) has been described as a metabolic disease as metabolic alterations are common in disparate RCC etiologies. Extracellular vesicles (EVs), the lipid bilayer-enclosed nanoparticles secreted by all living cells, have emerged as crucial mediators of intercellular and inter-organ communication, capable of shuttling functional proteins, lipids, and nucleic acids between cells. This review summarizes the essential events in tumor-associated metabolic reprogramming with a particular focus on renal cancers. We further explore how EVs released by metabolically deranged cells in cancer with altered cargos reprogram the renal cellular landscape, fostering tumor initiation, proliferation, angiogenesis, immune evasion, and therapy resistance. Understanding this EV-mediated axis not only elucidates the pathophysiological link between these conditions but also helps to unveil novel potential therapeutic targets for RCC patients.