Targeting CBX3 by a dual BET/PLK1 inhibitor enhances the anti-tumor efficacy of CDK4/6 inhibitors in prostate cancer

The BET inhibitors and CDK4/6 inhibitors have shown efficacy in preclinical models of prostate cancer. We previously reported that CDK4/6 inhibitors overcome the resistance of CRPC to BET inhibitors by destabilizing BRD4, which indicates that the combination of CDK4/6 inhibitors and BET inhibitors is also promising for the treatment of CRPC.

In this study, we attempted to exploit the candidates affecting the antitumor activity of CDK4/6 inhibitors and BET inhibitors in CRPC. Our data demonstrated that CBX3 is almost positively correlated with the cell cycle of multiple malignancies and is downregulated by BET inhibitors. Then, we showed that CBX3 is transcriptionally upregulated by BRD4 in CRPC cells.