AKT1 and renal carcinoma: An important reason that was postulated for the inferior outcomes compared with everolimus in the renal cancer study was the relief of feedback inhibition of receptor tyrosine kinase signalling through initial AKT inhibition caused by mTORC2 inhibition, leading to subsequent reactivation of AKT and inhibitory downstream phosphorylation of targets including the pro-apoptotic FOXO transcription factors26,27.