Title: Mechanisms of drug resistance that target the androgen axis in castration resistant prostate cancer (CRPC).
Authors: Penning, Trevor M
Published In J Steroid Biochem Mol Biol, (2015 Sep)
Abstract: Castrate resistant prostate cancer (CRPC) is the fatal-form of prostate cancer and remains androgen dependent. The reactivation of the androgen axis occurs due to adaptive intratumoral androgen biosynthesis which can be driven by adrenal androgens and/or by changes in the androgen receptor (AR) including AR gene amplification. These mechanisms are targeted with P450c17 inhibitors e.g., abiraterone acetate and AR super-antagonists e.g., enzalutamide, respectively. Clinical experience indicates that with either agent an initial response is followed by drug resistance and the patient clinically progresses on these agents. This article reviews the mechanisms of intrinsic and acquired drug resistance that target the androgen axis and how this might be surmounted.
PubMed ID: 26032458
MeSH Terms: Androgen Receptor Antagonists/pharmacology; Androgen Receptor Antagonists/therapeutic use; Androgens/metabolism*; Androstenes/pharmacology; Androstenes/therapeutic use; Animals; Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use; Drug Resistance, Neoplasm*/drug effects; Humans; Male; Phenylthiohydantoin/analogs & derivatives; Phenylthiohydantoin/pharmacology; Phenylthiohydantoin/therapeutic use; Prostate/drug effects*; Prostate/metabolism; Prostate/pathology; Prostatic Neoplasms, Castration-Resistant/drug therapy*; Prostatic Neoplasms, Castration-Resistant/genetics; Prostatic Neoplasms, Castration-Resistant/metabolism; Receptors, Androgen/genetics; Receptors, Androgen/metabolism