The mutated androgen receptor and its implications for the treatment of metastatic carcinoma of the prostate.

Androgen deprivation is the most effective therapy for patients with advanced prostatic carcinoma. The lack of androgen stimulation on these cells causes them to become apoptotic. Although therapeutic efficacy of initial androgen deprivation in prostate cancer is high, the emergence of androgen-independent cancer is inevitable. Withdrawal of the antiandrogen flutamide elicits surprising activity in these cancers. In numerous studies the response rates cell line harbors a mutation in codon 877 of the androgen receptor. The mutant receptor loses androgen specificity and is activated by various steroids as well as flutamide. Identical and similar mutations have now been isolated from human prostate cancer tissue. The discovery of the mutated androgen receptor sheds light on the emergence of androgen-independent cancer and should facilitate the development of more efficacious therapies.