Abnormal activation of mammalian target of rapamycin (mTOR) pathway is an important target for development of anti-cancer drug, the most common mechanism of mTOR activation in breast cancer is via phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling, PI3K/AKT/mTOR pathway is closely associated with cellular resistance to CDK4/6 inhibitors (15, 68–70). Here, CDK4 is linked to cancer.