AKT1 and nonpapillary renal cell carcinoma: In fact, despite the fact that the overall mutation rate of PI3K/Akt pathway in ccRCC is relatively low, the overall activation of PI3K/Akt in ccRCC is high compared to other cancers, suggesting that the dyregulation of the PI3K/Akt pathway in ccRCC could be a consequence of epigenetic mechanisms mediated by EVs [52,53,54].