Format

Send to

Choose Destination
Urol Oncol. 2015 Jun;33(6):280-8. doi: 10.1016/j.urolonc.2014.12.017. Epub 2015 Mar 18.

Enzalutamide: Development from bench to bedside.

Author information

1
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
2
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: Scherh@mskcc.org.

Abstract

Prostate tissue, whether benign or malignant, is heavily dependent on androgen receptor (AR) signaling for growth and proliferation. Androgen deprivation therapy has been standard of care for management of metastatic prostate cancer for the past 70 years. AR antagonists were developed to further abrogate signaling through this pathway by competitive inhibition of the receptor. First-generation compounds such as bicalutamide had modest efficacy, and in the setting of AR overexpression or specific mutations in the AR ligand-binding domain, these early compounds had partial agonist properties that could stimulate tumor growth. Enzalutamide was developed to overcome these deficiencies, and here, we present the story of its preclinical discovery, clinical development, and ultimate approval as a standard-of-care therapy for castration-resistant prostate cancer. Also discussed are ongoing efforts to elucidate mechanisms of resistance to this agent as well as studies that are investigating its role in other prostate cancer disease states and other cancer types.

KEYWORDS:

AR targeted therapies; Enzalutamide; MDV3100; Prostate cancer; castration resistant prostate cancer

PMID:
25797385
DOI:
10.1016/j.urolonc.2014.12.017
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center