The precise mechanism coordinating this feedback is up for debate and could involve transcriptional regulation of mTOR repressors TSC Complex Subunit 1 and 2 (TSC1/2) by AR (58), deactivation of the tumor suppressor phosphatase PH Domain And Leucine Rich Repeat Protein Phosphatase 1 (PHLPP1) (59), reactivation of AKT via mTORC2 (36), or reactivation of insulin receptor substrate 1. Therefore, it is expected that most mTOR inhibitors as monotherapies have not succeeded past phase 2 clinical trials in PCa. This evidence concerns the gene IRS1 and posterior cortical atrophy.