CDK4 and breast cancer: For instance, Cai et al. (2023) demonstrated in breast cancer models that palbociclib (a CDK4/6 inhibitor) induced significant upregulation of cyclin-dependent kinase regulators (CDK4, Cyclin D1, Cyclin E1), which mechanistically activated the PI3K/AKT/mTOR axis through a feedback loop involving Cyclin D1 overexpression.