To our knowledge, this is the first report showing that: (1) RB-deficient or inactive tumor cells are more sensitive to MCMs reduction; (2) statin drug SVA or ARO inhibits the protein expression of licensing factor MCM7 and RB via activating ER and autophagy signaling pathway; (3) SVA or ARO induces a higher apoptosis rate in RB-deficient cells than in RB-proficient cells; (4) SVA or ARO triggers DDR checkpoint cascade at earlier time point and induces more chromosome breaks or gaps in RB-deficient tumor cells than in RB-proficient tumor cells. This evidence concerns the gene RB1 and neoplasm.