title: Castration-resistant prostate cancer: adaptive responses in the androgen axis.
abstract: The androgen signaling axis in prostate cancer is associated with multiple adaptive mechanisms in response to castration. Herein we review these adaptations with an emphasis on recent molecular insights into the growth and development of castration resistant prostate cancer (CRPC). Alterations include both conventional and novel intracrine androgen synthesis pathways and androgen transport as well as androgen receptor (AR) overexpression, mutation, and splice variation. Each of these underlying mechanisms are potentially linked to post-castration growth, especially after treatment with newer hormonal agents such as abiraterone and enzalutamide. Post-translational AR modifications are well documented and these can affect receptor activity, stability, localization, and interaction with other proteins. Changes in recruitment of androgen receptor associated co-activators/repressors and a distinct AR-induced transcriptional program can dramatically alter proliferation, invasion, and metastasis in a ligand and context-dependent manner. Numerous previously uncharacterized non-coding RNAs, some of which are androgen regulated, may also have important biological function in this disease. Taken together, the view of CRPC has changed dramatically in the last several years. This has occurred not only within the setting of multiple treatment paradigm changes, but also as a multiplicity of potential molecular mechanisms underlying this disease state have been explored and discovered.
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Egan
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA; Department of Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA; National Engineering Laboratory for AIDS Vaccine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA; Department of Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA; Department of Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Life Sciences, Jilin University, China and Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Balk
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA; Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA; Department of Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA. Electronic address: osartor@tulane.edu.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002369:Castration; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal
keywords: Adaptive signaling; Androgen receptor; Castrate-resistance; Prostate cancer