Androgen receptor variation affects prostate cancer progression and drug resistance

• Published in: Pharmacological research Vol. 114; pp. 152 - 162
• Main Authors: McCrea, Edel, Sissung, Tristan M., Price, Douglas K., Chau, Cindy H., Figg, William D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2016
• Subjects: Androgen receptor; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; AR-V7; Disease Progression; Drug Resistance, Neoplasm; Genetic Variation; Genotype; Humans; Male; Mutation; Pharmacology; Prostate - drug effects; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Receptors, Androgen - genetics; Pharmacology; Mutation; AR-V7; Prostate cancer; Androgen receptor
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2016.10.001

[Display omitted] Significant therapeutic progress has been made in treating prostate cancer in recent years. Drugs such as enzalutamide, abiraterone, and cabazitaxel have expanded the treatment armamentarium, although it is not completely clear which of these drugs are the most-effective option for individual patients. Moreover, such advances have been tempered by the development of therapeutic resistance. The purpose of this review is to summarize the current literature pertaining to the biochemical effects of AR variants and their consequences on prostate cancer therapies at both the molecular level and in clinical treatment. We address how these AR splice variants and mutations affect tumor progression and therapeutic resistance and discuss potential novel therapeutic strategies under development. It is hoped that these therapies can be administered with increasing precision as tumor genotyping methods become more sophisticated, thereby lending clinicians a better understanding of the underlying biology of prostate tumors in individual patients.