Prostate cancer is often responsive to treatment with drugs that block the androgen receptor. This treatment is effective until the tumour adapts and no longer requires androgen receptor function in cancer progression. So-called androgen, or castration, resistant forms of prostate cancer are the most deadly. A common mechanism that allows prostate cancer to become androgen resistant is one in which the cancer cells extensively change their identity such that they no longer even express the androgen receptor. This proposal seeks to understand how this transformation takes place.