CDK4 and cancer: The initial increase in sphere formation after palbociclib treatment in PDSs may instead be influenced by strong proliferative inhibition by the drug followed by a temporary proliferative rebound effect that could be due to phosphorylation of the CDK4/6 target retinoblastoma protein by other CDKs, such as CDK2, that could cause cancer cells to enter in S-phase, despite inhibition by palbociclib36.