Exploiting epigenetic targets to overcome taxane resistance in prostate cancer.

ABSTRACT: The development of taxane resistance remains a major challenge for castration resistant prostate cancer (CR-PCa), despite the effectiveness of taxanes in prolonging patient survival. To uncover novel targets, we performed an epigenetic drug screen on taxane (docetaxel and cabazitaxel) resistant CR-PCa cells. We identified BRPF reader proteins, along with several epigenetic groups (CBP/p300, Menin-MLL, PRMT5 and SIRT1) that act as targets effectively reversing the resistance mediated by ABCB1. Targeting BRPFs specifically resulted in the resensitization of resistant cells, while no such effect was observed on the sensitive compartment. These cells were successfully arrested at the G₂/M phase of cell cycle and underwent apoptosis upon BRPF inhibition, confirming the restoration of

SUBMITTER: Cevatemre B 

PROVIDER: S-EPMC10861560 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature