title: Androgen receptor aberrations in the era of abiraterone and enzalutamide.
abstract: Prostate cancer is the most prevalent non-skin cancer and the second leading cause of cancer death in men of the western world. As growth and differentiation of prostate cancer largely depend on androgens, inhibition of the androgen/androgen receptor signaling axis is the main treatment for locally advanced and/or metastatic tumors. Although first-line androgen deprivation therapies like chemical/surgical castration and/or administration of anti-androgens are able to control the disease for several years, prostate cancer almost invariably recurs as castration-resistant prostate cancer. This stage of the disease is characterized by a sustained AR-signaling despite castrate levels of circulating androgens. Various molecular mechanisms were shown to induce castration resistance. This review will discuss the most recent and relevant experimental findings on AR-signaling in castration-resistant prostate cancer in order to provide a comprehensive interpretation of the clinical behavior of this tumor entity following treatments with abiraterone, enzalutamide, ARN-509 or taxanes.
authors.affiliation: Department of Urology, Ulm University Medical Center, Prittwitzstrasse 43, 89075, Ulm, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Jentzmik
authors.affiliation: Department of Urology, Ulm University Medical Center, Prittwitzstrasse 43, 89075, Ulm, Germany.
authors.forename: Anca
authors.initials: A
authors.lastname: Azoitei
authors.affiliation: Department of Urology, Ulm University Medical Center, Prittwitzstrasse 43, 89075, Ulm, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Zengerling
authors.affiliation: Department of Urology, Ulm University Medical Center, Prittwitzstrasse 43, 89075, Ulm, Germany.
authors.forename: Ilija
authors.initials: I
authors.lastname: Damjanoski
authors.affiliation: Department of Urology, Ulm University Medical Center, Prittwitzstrasse 43, 89075, Ulm, Germany. marcus.cronauer@uni-ulm.de.
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Cronauer
mesh_terms: D000736:Androstenes / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C410798:AR protein, human; D000736:Androstenes; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D010669:Phenylthiohydantoin; C540278:enzalutamide; C089740:abiraterone
keywords: AR-point mutations; AR-variants; Abiraterone; Enzalutamide; Personalized medicine