However, insights into the biology of prostate cancer have shown that up to 60% of patients with advanced disease have clinically actionable molecular alterations in non-AR-related pathways.8 In particular, mutations in the genes encoding components of the DNA damage response (DDR; Box 1), such as BRCA1 and BRCA2, are common in prostate cancer8–13 Such mutations reduce the ability to effectively repair single- and double-strand DNA damage, and thus compromise genomic integrity. The gene discussed is AR; the disease is Familial prostate cancer.