Prostate cancer patients are often given androgen deprivation therapies (ADT) that block the function of the signaling protein, androgen receptor (AR). While effective initially, tumors typically transform into a more aggressive disease known as castration resistant prostate cancer (CRPC) while on ADT. One major cause of resistance in CRPC is thought to be the emergence of Androgen Receptor variants (AR-Vs) at the genomic level. AR-Vs are altered forms of AR that are not sensitive to these drugs. This proposal aims to develop a high through put platform that can identify at the protein level which AR-Vs are present in clinical samples including tumor tissues and Circulating Tumor Cells (CTCs). Recent evidence from this grant suggests that there are three novel AR-Vs expressed at the protein level which was not previously known in PCa cell lines and in LuCaP Patient derived xenografts. Our results indicates that the presence of AR-Vs might contribute to the ADT resistance and provides rational to further our investigation and identify if these variants are involved mechanistically in drug resistance and open avenues to develop new treatments approaches.