METODOS PARA DETERMINAR RESISTENCIA A TERAPIA DE RECEPTOR DE ANDROGENO

La presente invencion describe una proteina de fusion que comprende un polipeptido del receptor de androgeno (AR) o una variante de este que tiene actividad del AR que comprende una modificacion en una posicion de aminoacido que corresponde a la posicion de aminoacido 876 de la secuencia de aminoacidos que se expone en SEQ ID NO: 1, donde dicho polipeptido AR se fusiona a un polipeptido heterologo, una secuencia de senal de secrecion, una etiqueta de epitopo o una etiqueta de afinidad. Tambien se refiere a un acido nucleico, un vector, una celula huesped, un microchip, y un sistema para detectar un AR modificado Described herein are modified androgen receptor polypeptides that are resistant to inhibition by an androgen receptor inhibitor. Described herein are compositions, combinations, and kits containing the modified androgen receptor polypeptides and methods of using the modified androgen receptor polypeptides. Also described herein are methods of using the modified androgen receptor polypeptides as screening agents for the identification and design of 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 that include the compounds described herein, as well as methods of using such androgen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions, including cancers, such as castration resistant prostate cancers, that are mediated or dependent upon androgen receptors.