Dr. Taplin on the Mechanism of Action of Enzalutamide
Mary-Ellen Taplin, MD
Published Online: Thursday, November 29, 2012
Mary-Ellen Taplin, MD, associate professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute, discusses the unique mechanism of action (MOA) for the androgen receptor antagonist enzalutamide (Xtandi; MDV3100), which was recently approved by the FDA for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel.
The mechanism of action for the agent enzalumatide makes it a fantastic antiandrogen and sets it apart from older agents such as bicalutamide and nilutamide, explains Taplin. The agent is able to inhibit androgen receptor nuclear translocation rather than competing with androgen in the cytoplasm. Blocking entry into the nucleus prevents gene transcription and the activation of growth factors. Taplin believes this unique MOA is likely the reason that enzalutamide is efficacious in patients with mCRPC following chemotherapy.
The optimal way to sequence this agents is an important question that still needs answered. As a result, researchers are currently examining the administration of enzalutamide in early-stage prostate cancer and combination strategies.