| abstract |
Described herein are modified androgen receptor polypeptides that are resistant to inhibition by androgen receptor inhibitors. Described herein are compositions, combinations and kits containing the modified androgen receptor polypeptides, as well as methods of using the modified androgen receptor polypeptides. Also described herein are methods of using the modified androgen receptor polypeptides as screening agents to identify and design third-generation androgen receptor modulators. Also described herein are third-generation androgen receptor modulators that inhibit the activity of the modified androgen receptor polypeptides. Also described are pharmaceutical compositions and medicaments comprising the compounds described herein, as well as methods of using such androgen receptor modulators, alone or in combination with other compounds, for the treatment of diseases or disorders comprising androgen receptor body-mediated or androgen receptor-dependent cancers, such as castration-resistant prostate cancer. |