OncoTargets and Therapy
Open access peer-reviewed scientific and medical journals.
Dove Medical Press is now a member of the Open Access Initiative
An Author's Guide
A guide to help authors get their paper published.
Support Open Access and Dove Press
Promotional Article Monitoring - further details
Favored Author Program
Real benefits for authors, including fast-track processing of papers.
Clinical appraisal of abiraterone in the treatment of metastatic prostatic cancer: patient considerations, novel opportunities, and future directions
(3837) Total Article Views
Authors: Bedoya DJ, Mitsiades N
Published Date January 2013
Volume 2013:6 Pages 9 - 18
|Received:||25 September 2012|
|Accepted:||23 November 2012|
|Published:||03 January 2013|
1Clearview Cancer Institute, Huntsville, AL, USA; 2Department of Medicine, 3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
Abstract: While androgen-deprivation therapy can induce dramatic clinical responses in advanced and metastatic prostate cancer, refractory disease (castration-resistant prostate cancer [CRPC]) eventually emerges. In recent years, several studies have demonstrated the importance of residual intratumoral androgens in maintaining androgen receptor (AR) transcriptional activity in CRPC. The cytochrome P450 enzyme CYP17 is an obligatory step in androgen synthesis, and therefore a critical therapeutic target in CRPC. Abiraterone acetate is a selective, irreversible inhibitor of CYP17 and can suppress adrenal synthesis of androgen precursors, and possibly in situ steroidogenesis in the tumor microenvironment. In a phase III multicenter study, abiraterone in combination with prednisone improved median overall survival of men with docetaxel-refractory CRPC by 3.9 months compared to placebo plus prednisone, and also resulted in higher objective prostate-specific antigen and radiographic response rates. The study led to the FDA approval in April 2011 of abiraterone for treatment of chemotherapy-refractory CRPC patients, validating steroidogenesis and the AR axis in general as therapeutic targets in CRPC. The FDA indication for abiraterone was expanded to all CRPCs in December 2012, while evaluation in even earlier disease states is ongoing. We propose a comprehensive AR axis-targeting approach via simultaneous, frontline enzymatic blockade of several steroidogenic enzymes (eg, CYP17 and AKR1C3) in combination with gonadotropin-releasing hormone analogs and potent, second-generation AR antagonists (eg, enzalutamide) in order to improve outcomes in patients with prostate cancer.
Keywords: androgen synthesis, testosterone, dihydrotestosterone, CYP17, AKR1C3, MDV3100 (enzalutamide)
Cannotea Citeulike Del.icio.us Facebook LinkedIn Twitter
Readers of this article also read:
- Have an opinion about one of our articles?
We encourage you to write a letter to the editor.
- The bradykinin B2 receptor induces multiple cellular responses leading to the proliferation of human renal carcinoma cell lines
- Epigenomics in cancer management
- Serous endometrial intraepithelial carcinoma: a case series and literature review
- Intercellular cancer collisions generate an ejected crystal comet tail effect with fractal interface embryoid body reassembly transformation