Targeting Prostate Cancer with Bifunctional Modulators of the Androgen Receptor

Abstract : The overall goal of this research project is to develop and implement a conceptually innovative strategy for down-regulating nuclear receptors such as the androgen receptor: the creation of bifunctional molecules that simultaneously bind to the nuclear receptor and to chromatin-modifying enzymes and/or complexes. In this way, genes that are typically regulated by androgen receptor and glucocorticoid receptor will be extrinsically controlled. In this final year of funding, we completed the functional characterization of agonist and antagonist-based bi-functional recruiters. Importantly, we have a suite of recruiters that show context specificity. In the extension period of the work, we completed RNAseq experiments to gain a complete understanding of the context specificity of this exciting class of molecules.