PIK3CA and cancer: Under normal conditions, feedback regulation from mTOR complex 1 (mTORC1)/S6K1 to insulin receptor substrate-1 (IRS-1) attenuates cell growth signals.5, 6, 7 In addition, S6K1 phosphorylates rictor and reduces mTOC2 signaling.8 In some cancer cells treated with rapalogs, these two feedback loops can enhance PI3K/Akt signaling.