Cell line model of enzalutamide resistant prostate cancer
Traditionally, AR drug discovery has used both ligand and AR structure-based design, seeking antagonists by classical ligand binding assays or cellular reporter assays that assess functional antagonism of androgen-dependent transcriptional activation. While these largely empirical approaches have yielded clinically useful drugs, they share a remarkable degree of structural, functional and mechanistic similarity. Not surprisingly then, de novo resistance or the rapid development of resistance has emerged as an impediment to durable clinical response in PCa patients. For this invention, we engineered cell lines that model castration resistant prostate cancer and can therefore be used to identify novel chemical entities that may be predicted to have efficacy in resistant disease.