Plk1 Inhibition Enhances the Efficacy of BET Epigenetic Reader Blockade in Castration-Resistant Prostate Cancer.

ABSTRACT: Polo-like kinase 1 (Plk1), a crucial regulator of cell-cycle progression, is overexpressed in multiple types of cancers and has been proven to be a potent and promising target for cancer treatment. In case of prostate cancer, we once showed that antineoplastic activity of Plk1 inhibitor is largely due to inhibition of androgen receptor (AR) signaling. However, we also discovered that Plk1 inhibition causes activation of the β-catenin pathway and increased expression of c-MYC, eventually resulting in resistance to Plk1 inhibition. JQ1, a selective small-molecule inhibitor targeting the amino-terminal bromodomains of BRD4, has been shown to dramatically inhibit c-MYC expression and AR signaling, exhibiting antiproliferative effects in a range of cancers. Because c-MYC and AR signaling are es

SUBMITTER: Mao F 

PROVIDER: S-EPMC6030429 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature