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. The gene discussed is CDK4; the disease is neoplasm.