Author(s): Taplin ME
Androgen receptor (AR) signaling is necessary for the development of prostate cancer. Androgen-deprivation therapy (ADT) for prostate cancer was described over 50 years ago and ADT remains the mainstay of systemic therapy. AR signaling remains intact as the disease evolves to castration-resistant prostate cancer (CRPC). Through cellular adaptations, CRPC continues to rely on androgens and AR growth signaling, and thus AR remains an important therapeutic target. CRPC cells upregulate enzymes used in androgen synthesis, thus providing an intracellular source of androgen despite systemic castration. Compounds in development, such as antiandrogens, lyase inhibitors, heat-shock protein-90 inhibitors, histone deacetylase inhibitors and others, will provide new tools to more effectively reduce ligand, inhibit AR and/or inhibit costimulatory pathways and result in improved clinical outcomes.