PIK3CA and cancer: While rapamycin has been previously shown to reduce SASP without reversing the senescence-induced growth arrest in human fibroblasts [61,62], in certain contexts – particularly in cells with activation of the PI3K-AKT-MTOR signaling pathway, such as certain cancer cells and aVICs – selective inhibition of MTOR-RPS6KB1 signaling can trigger AKT activation through a negative feedback loop from RPS6KB1 to IRS1-PI3K-AKT.