Intriguingly, palbociclib interacts with the TGF-β pathway through blocking CDK4-mediated inactivation of SMAD2; in T47D breast cancer cells, palbociclib enhanced SMAD2 binding to the genome by reducing its inhibitory phosphorylation by CDK4/6, resulting in enhanced expression of TGF-β target genes CDKN2B and PMEPA1 [51]. This evidence concerns the gene CDK4 and breast cancer.