However, several studies investigated the dual negative feedback loop in a variety of human cancers: mTOR/S6K activation attenuates upstream phosphatidylinositol 3-kinase (PI3K) pathway activation, while treatment with mTOR inhibitors (rapamycin and its analogs) lead to a hyperactive insulin receptor substrate 1 (IRS-1)/PI3K pathway. This evidence concerns the gene IRS1 and cancer.