By further examining changes in the PI3K/AKT/mTOR pathway looking at the downstream transcription factors S6K and eIF4E, and PRAS40 (inhibits mTOR and IRS-1), we could identify their role in the negative feedback of the PI3K pathway, an effect commonly seen in various cancers and cancer models (27, 34–36). The gene discussed is EIF4E; the disease is cancer.