Selection for androgen receptor mutations in prostate cancers treated withandrogen antagonist

The role of androgen receptor (AR) mutations in androgen-independent prosta te cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases, Mutations were found in 5 of 16 pa tients who received combined androgen blockade,vith the AR antagonist fluta mide, and these mutant ARs were strongly stimulated by flutamide, In contra st, the single mutant AR found among 17 patients treated with androgen abla tion monotherapy was not flutamide stimulated. Patients with flutamide-stim ulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs, These findings demonstrate that AR mutations occur in response to strong: selective pressure from flutamide treatment.