Molecular mechanisms of enzalutamide resistance in prostate cancer

Eliot B Blatt; Ganesh V Raj

doi:10.20517/cdr.2019.25

Molecular mechanisms of enzalutamide resistance in prostate cancer

Cancer Drug Resist. 2019 Jun 19;2(2):189-197. doi: 10.20517/cdr.2019.25. eCollection 2019.

Authors

Eliot B Blatt¹, Ganesh V Raj^{1

2}

Affiliations

¹ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
² Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

An estimated 30,000 men in the United States will die of metastatic prostate cancer (PCa) each year due to the development of therapy resistance, most notably resistance to second-generation antiandrogen enzalutamide. The vast majority of PCa is driven by the androgen receptor (AR). Enzalutamide is an AR antagonist, which extends patient survival and is widely used in the clinic for the treatment of castration-resistant prostate cancer (CRPC); however, many patients will have primary or develop acquired resistance and continue to progress. Characterization of the molecular mechanisms of enzalutamide resistance provides insight into potentially efficacious therapies for enzalutamide-resistant CRPC (ER-CRPC). Understanding these mechanisms is critical for the identification of biomarkers predictive of therapy resistance and the development of therapeutic strategies to target ER-CRPC.

Keywords: Drug resistant cancers; biomarkers of drug responsiveness; resistance modulation; targeted therapy resistance.

Publication types

Review