Single-arm studies have demonstrated preliminary signs of efficacy for intermittent pharmacologic dose testosterone (i.e. Bipolar Androgen Therapy; BAT) in treating advanced prostate cancer. In this project, we will conduct detailed molecular assessments on biospecimens (i.e. blood, metastatic tissue) from men receiving BAT to determine somatic and germline factors that predict for response/resistance. We will also evaluate additional PDT-based regimens (e.g. combinatorial treatments) in preclinical models. This annual technical progress report details progress made during the first year of funding for this project (30 Sep 2018 1 Oct2019). During Year 3 we have continued to collect biospecimens from men enrolled to studies testing BAT. We have published correlative research showing responses to BAT are enriched in patients with mutations in DNA damage repair (DDR) genes. Preclinical studies have supported the hypothesis that DDR abnormalities predict for response to BAT and have also shown that responses are enhanced when BAT is given in combination with PARP inhibition.