To date, several prospective studies in patients with PTEN inactivation due to somatic and germline PTEN mutations have failed to demonstrate a clinical benefit for various agents targeting the PI3K/AKT/mTOR signaling pathway: for example, a phase II trial of the allosteric AKT inhibitor MK-2206 in patients with advanced breast cancer who had tumors with PIK3CA/AKT1 mutations and/or PTEN loss/mutation found that this agent had limited clinical and PD activity as monotherapy, and the study was stopped early due to futility [30]. Here, PTEN is linked to breast cancer.