Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist.

作者：Mary‐Ellen Taplin, Glenn J. Bubley, Yoo‐Joung Ko, Eric Jay Small, Melissa P. Upton, Barur R. Rajeshkumar, Steven P. Balk · 发表于：PubMed · 年份：1999 · 被引用次数：598 · 研究领域：Prostate Cancer Treatment and Research、Sexual Differentiation and Disorders、Prostate Cancer Diagnosis and Treatment

The role of androgen receptor (AR) mutations in androgen-independent prostate 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 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated 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.