Notably, PTEN-deficiency in bladder cancer cells yielded disappointing results following rapamycin [41] or everolimus [42] treatment compared to cells expressing wild-type PTEN, likely because facilitation of AKT activation upon PTEN loss can have a more important role in driving the feedback loop in response to mTOR inhibition than in promoting the mTOR pathway. This evidence concerns the gene AKT1 and urinary bladder carcinoma.