Abstract: This disclosure describes markers that can identify patients at risk of developing castration-resistant prostate cancer. The markers, and analyses that use the markers, can be used by health professionals to guide treatment decisions by, for example, helping to evaluate the likelihood that a patient will respond to or develop resistance to prostate cancer therapies targeted to the androgen receptor. Thus, in some cases, methods described herein may be used to identify subjects under treatment for prostate cancer as at risk for developing castration-resistant prostate cancer. Such an evaluation may indicate that a change in prescribed therapy is appropriate. In some of these instances, the change may involve modifying the subject's treatment regimen to include administration of a pharmaceutical composition effective for treating castration-resistant prostate cancer before resistance to androgen receptor-based treatments develops.