CDK4 and breast cancer: Importantly, PARP’s small-molecule compound inhibitors disrupt the escape pathways of tumor cells and sustain DNA damage, leading to stagnation of tumor cells or cell death.[37,38] Since DNA repair is inhibited in G1/S phase cells, there are theoretical evidences for the efficacy of this combination therapy.[39] In conclusion, PARPis showed an exciting reversal of resistance in Rb-lost CDK4/6i resistant BC cells, the U.S. FDA has approved PARPis to treat ovarian cancer, but despite this, the molecular mechanism of how PARPis can achieve this reversal is still not clear.