AI Article Synopsis
- * It identifies that CBX3 is overexpressed in cells resistant to CDK4/6 inhibitors and plays a role in modulating the sensitivity of CRPC cells to these inhibitors by interacting with the RB1 protein.
- * The research suggests that targeting both BRD4 and PLK1 could enhance the effectiveness of treatment by affecting CBX3 and improving response to CDK4/6 inhibitors in CRPC cells.
Article Abstract
The development of castration-resistant prostate cancer (CRPC) is a significant factor that reduces life expectancy among patients with prostate cancer. Previously, it is reported that CDK4/6 inhibitors can overcome the resistance of CRPC to BET inhibitors by destabilizing BRD4, suggesting that the combination of CDK4/6 inhibitors and BET inhibitors is a promising approach for treating CRPC. In this study, candidates that affect the combined antitumor effect of CDK4/6 inhibitors and BET inhibitors on CRPC is aimed to examine. The data demonstrates that CBX3 is abnormally upregulated in CDK4/6 inhibitors-resistant cells. CBX3 is almost positively correlated with the cell cycle in multiple malignancies and is downregulated by BET inhibitors. Mechanistically, it is showed that CBX3 is transcriptionally upregulated by BRD4 in CRPC cells. Moreover, it is demonstrated that CBX3 modulated the sensitivity of CRPC to CDK4/6 inhibitors by binding with RB1 to release E2F1. Furthermore, it is revealed that PLK1 phosphorylated CBX3 to enhance the interaction between RB1 and CBX3, and desensitize CRPC cells to CDK4/6 inhibitors. Given that BRD4 regulates CBX3 expression and PLK1 affects the binding between RB1 and CBX3, it is proposed that a dual BRD4/PLK1 inhibitor can increase the sensitivity of CRPC cells to CDK4/6 inhibitors partially through CBX3.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754129 | PMC |
| http://dx.doi.org/10.1002/advs.202302368 | DOI Listing |
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