We also found that several resistant clones became hypersensitive to mTOR inhibitors [i.e., everolimus (13/29 clones), and rapamycin (6/29 clones)] (Figure 2B), which is consistent with previous findings from breast cancer studies that investigated whether targeting activated PI3K/mTOR signaling may overcome acquired resistance to CDK4/6-based therapies (21–23). Here, CDK4 is linked to breast cancer.