Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of therapeutic options but from the limited duration of clinical and survival benefit offered by treatments in this setting due to primary and acquired resistance. The remarkable molecular heterogeneity and tumor adaptability in advanced prostate cancer necessitate optimization of such treatment strategies. While the future of CRPC management will involve newer targeted therapies in deliberately biomarker-selected patients, interventions using current approaches may exhibit improved clinical benefit if employed in the context of optimal sequencing and combinations. This review outlines our current understanding of mechanisms of therapeutic resistance in progression to and after the development of castration resistance, highlighting targetable and reversible mechanisms of resistance.
Current oncology reports. 2017 Feb [Epub]
Mary Nakazawa, Channing Paller, Natasha Kyprianou
Departments of Urology, Molecular and Cellular Biochemistry, Pathology and Toxicology and Cancer Biology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA., Departments of Urology, Molecular and Cellular Biochemistry, Pathology and Toxicology and Cancer Biology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA. .