CDK4 and breast carcinoma: Results showed that palbociclib combined with everolimus acted synergistically in ribosomal protein S6 kinase beta 1(S6K1)-amplified breast cancer PDO models, and they proved in PDX models that adding an mTOR inhibitor significantly reduced the levels of phosphorylated retinoblastoma gene(p-Rb) and cyclin D1 in tumors overexpressing S6K1, finding that S6K1 amplification is an important mechanism for inherent resistance of breast cancer to palbociclib (CDK4/6 inhibitor) (82).