Current Urology Reports

, 17:29 | Cite as

Novel Insights into Molecular Indicators of Response and Resistance to Modern Androgen-Axis Therapies in Prostate Cancer

  • John L. Silberstein
  • Maritza N. Taylor
  • Emmanuel S. AntonarakisEmail author
Prostate Cancer (A Kibel, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Prostate Cancer


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. 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.


Prostate cancer Androgen receptor Splice variants Resistance Biomarker 



androgen deprivation therapy


androgen receptor


androgen response element


full-length androgen receptor


androgen receptor splice variant


cell-free DNA


castration-resistant prostate cancer


circulating tumor cell


cytochrome P450 17A1


DNA-binding domain




glucocorticoid receptor


hormone-sensitive prostate cancer


ligand-binding domain


N-terminal domain


progression-free survival


progesterone receptor


overall survival


Compliance with Ethical Standards

Conflict of Interest

John L. Silberstein and Maritza N. Taylor declare no potential conflicts of interest. Emmanuel S. Antonarakis has served as a paid consultant/advisor for Janssen, Astellas, Sanofi, Dendreon, Essa, and Medivation; he has received research funding from Janssen, Johnson & Johnson, Sanofi, Dendreon, Exelixis, Genentech, Novartis, and Tokai; he is a co-inventor of a technology that has been licensed to Tokai.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • John L. Silberstein
    • 1
  • Maritza N. Taylor
    • 1
  • Emmanuel S. Antonarakis
    • 2
    Email author
  1. 1.Brady Urological Institute, Department of UrologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of OncologyJohns Hopkins University School of MedicineBaltimoreUSA

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