Treatment of metastatic castration-resistant prostate cancer (mCRPC) with enzalutamide

•Enzalutamide has efficacy in mCRPC patients with and without prior chemotherapy.•Trials of enzalutamide are ongoing in hormone-naïve and nonmetastatic CRPC patients.•Cross-resistance may occur between enzalutamide and other AR inhibitors and taxanes.•AR mutations, splice variants, and expression changes may also induce resistance.•Use of enzalutamide in combination with other therapies is being investigated.

Prostate cancer is initially responsive to androgen deprivation therapy, but most patients eventually develop castration-resistant disease. Enzalutamide is an androgen receptor (AR) inhibitor that targets several steps in the AR signaling pathway and has shown significant efficacy in the treatment of metastatic castration-resistant prostate cancer in patients with or without prior chemotherapy. To provide optimal treatment, it is important to understand the implications of enzalutamide use in the context of other therapies, as recent findings have suggested cross-resistance occurs between and within drug classes. Mutations and splice variants of AR also impact the course of prostate cancer. Future strategies involving enzalutamide should account for previous exposure to taxanes or antiandrogen therapies and the presence of AR variants that could affect efficacy.