While androgen ablation remains a mainstay for advanced prostate cancer therapy, nearly all patients will inevitably develop disease escape with time. Upon the development of castration-resistant prostate cancer, other androgen-axis-targeted treatments may be added in an effort to starve the disease of its androgen signaling.
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Nevertheless, additional androgen-pathway resistance usually develops to these novel hormonal therapies. In this review, we will discuss the resistance mechanisms to modern androgen-axis modulators and how these alterations can influence a patient's response to novel hormonal therapy. We conceptualize these resistance pathways as three broad categories: (1) reactivation of androgen/AR-signaling, (2) AR bypass pathways, and (3) androgen/AR-independent mechanisms. We highlight examples of each, as well as potential therapeutic approaches to overcome these resistance mechanisms.
Current urology reports. 2016 Apr [Epub]
John L Silberstein, Maritza N Taylor, Emmanuel S Antonarakis
Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA.