Mechanisms of resistance to Androgen Receptor inhibition in prostate cancer

Division Of Basic Sciences - Nci

Investigators

Abstract

Prior studies investigating the interaction between PI3K pathway signaling and AR activity in cell lines and genetically engineered mouse models described a correlation between PTEN loss and decreased AR activity. We are using patient derived xenografts and organoid cultures from these lines to confirm the relevance to human disease, and to investigate the mechanism underlying reciprocal regulation of AR and PI3K activity. We have created inducible knockdown and expression constructs that will be used in this study, and optimized the transduction and culture conditions we will be using. We obtained approval of an animal protocol and have performed pilot in vivo experiments, laying the groundwork for future progress.