title: Novel Insights into Molecular Indicators of Response and Resistance to Modern Androgen-Axis Therapies in Prostate Cancer.
abstract: 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.
authors.affiliation: Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Silberstein
authors.affiliation: Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Maritza N
authors.initials: MN
authors.lastname: Taylor
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD 21287, USA.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Antonarakis
mesh_terms: D017398:Alternative Splicing; D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D011944:Receptors, Androgen
keywords: Androgen receptor; Biomarker; Prostate cancer; Resistance; Splice variants