Despite increasing evidence on the pivotal role of PI3K/Akt signaling in cancer, the strategies to hit PI3K/Akt/mTOR pathway have failed to demonstrate therapeutic activity in most ongoing clinical trials, and a previous phase II study testing perifosine in previously untreated patients with locally advanced, unresectable, or metastatic PDAC, was terminated as a result of unacceptable adverse events [66]. The gene discussed is MTOR; the disease is cancer.