CDK9 inhibition inhibits multiple oncogenic transcriptional and epigenetic pathways in prostate cancer.

ABSTRACT:

Background

Cyclin-dependent kinase 9 (CDK9) stimulates oncogenic transcriptional pathways in cancer and CDK9 inhibitors have emerged as promising therapeutic candidates.

Methods

The activity of an orally bioavailable CDK9 inhibitor, CDKI-73, was evaluated in prostate cancer cell lines, a xenograft mouse model, and patient-derived tumor explants and organoids. Expression of CDK9 was evaluated in clinical specimens by mining public datasets and immunohistochemistry. Effects of CDKI-73 on prostate cancer cells were determined by cell-based assays, molecular profiling and transcriptomic/epigenomic approaches.

Results

CDKI-73 inhibited proliferation and enhanced cell death in diverse in vitro and in vivo models of androgen receptor (AR)-driven and AR-independent models. Me

SUBMITTER: Rahman R 

PROVIDER: S-EPMC11405875 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature