Molecular determinants of response to high dose androgen therapy in prostate cancer

Clinical trials of high-dose androgen therapy for prostate cancer have shown promising efficacy but are limited by lack of criteria to identify likely responders. To elucidate factors that govern the growth-repressive effects of high-dose androgens we applied an unbiased integrative approach utilizing genetic screens and transcriptional profiling of prostate cancer cells with or without demonstrated phenotypic sensitivity to androgen-mediated growth repression. Through this comprehensive analysis, we identified genetic events and related signaling networks that determine the response to both high-dose androgen and androgen withdrawal. We applied these findings to develop a gene signature that may serve as an early indicator of treatment response and identify men with tumors amenable to high dose androgen therapy. RNA sequencing of human prostate tumor cell lines using Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.