IRS1 and cancer: Interestingly, some rapalogs amplified mTORC2-dependent Akt phosphorylation on Ser 473 and increased cell survival via inhibition of a negative feed-back loop based on mTORC1/p70S6K/IRS1/PI3K.40,41 It seems that combination of a PI3K inhibitor with an Akt inhibitor have greater antitumor activity in cancer treatment.