Clinical support for this hypothesis comes from the NeoPalAna study, where association between palbociclib resistance and persistent on-treatment expression of E2F targets (CCND3, CCNE1 and CDKN2D) was evident, indicating that continued activation of E2F transcription in resistant tumours, equates to loss of the RB regulon [35]. This evidence concerns the gene RB1 and neoplasm.