Prostate cancer is the most common cancer in men in the U.S. and the second most lethal. Nearly all prostate cancer deaths occur due to castration-resistant prostate cancer (CRPC) that has progressed despite androgen deprivation therapy (ADT). These therapies are designed to lower levels ofandrogens that can activate the androgen receptor (AR), the central protein in prostate cancer. We now know that androgens and androgen-dependent signaling pathways modulated by AR persist in CRPC cells despite ADT. However, until recently, effective agents to antagonize these persistent androgens and to disrupt AR signaling in CRPC cells were not available. MDV-3100 is a new antiandrogen that effectively inhibits androgen binding to and activation of AR in pre-clinical studies in CRPC cells. A phase l/ll clinical trial with MDV-3100 in CRPC patients also showed encouraging results, which led to the initiation of two ongoing phase III clinical trials. In this review, we will focus on its preclinical development and summarize the clinical results to date.
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