Targeting molecular resistance in castration-resistant prostate cancer.
Multiple mechanisms of resistance contribute to the inevitable progression of hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC). Currently approved therapies for CRPC include systemic chemotherapy (docetaxel and cabazitaxel) and agents targeting the resistance pathways leading to CRPC, including enzalutamide and abiraterone. While there is significant survival benefit, primary and secondary resistance to these therapies develops rapidly. Up to one-third of patients have primary resistance to enzalutamide and abiraterone; the remaining patients eventually progress on treatment. Understanding the mechanisms of resistance resulting in progression as well as identifying new targetable pathways remains the focus of current prostate cancer research. We review current knowledge of mechanisms of resistance to the currently approved treatments, development of adjunctive therapies, and identification of new pathways being targeted for therapeutic purposes.
Department of Urology, University of California, Davis, USA. tchandrasekar@ucdavis.edu.
Thenappan
T
Chandrasekar
Department of Urology, University of California, Davis, USA. jcyang@ucdavis.edu.
Joy C
JC
Yang
Department of Urology, University of California, Davis, USA. acgao@ucdavis.edu.
Allen C
AC
Gao
Department of Urology, University of California, Davis, USA. cpevans@ucdavis.edu.|, 4860 Y Street, Suite 3500, Sacramento, CA, 95817, USA. cpevans@ucdavis.edu.
Christopher P
CP
Evans
D018450:Disease Progression; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics*