Mechanisms of acquired resistance to androgen receptor targeting drugs in castration-resistant prostate cancer. Issue 11 (November 2014)

• Record Type: Journal Article
• Authors: Chism, David D; De Silva, Dinuka; Whang, Young E
• Is Part Of: Expert review of anticancer therapy. Volume 14:Issue 11(2014)
• Page Start: 1369
• Page End: 1378
• Publication Date: 2014-11
• Subjects: Cancer -- Treatment -- Periodicals; 616.99406
• DOI: 10.1586/14737140.2014.928594
• Languages: English
• ISSNs: 1473-7140

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>After initial response to androgen receptor (AR) targeting drugs abiraterone or enzalutamide, most patients develop progressive disease and therefore, castration resistant prostate cancer remains a terminal disease. Multiple mechanisms underlying acquired resistance have been postulated. Intratumoral androgen synthesis may resume after abiraterone treatment. A point mutation in the ligand-binding domain of AR may confer resistance to enzalutamide. Emergence of AR splice variants lacking the ligand-binding domain may mediate resistance to abiraterone and enzalutamide. Steroid receptors such as glucocorticoid receptor may substitute for AR. Drugs with novel mechanisms of action or combination therapy, along with biomarkers for patient selection, may be needed to improve the therapy of castration resistant prostate cancer.</p> </abstract>