Advanced prostate cancer eventually progresses and becomes castration resistant (CRPC) despite the fact that it is exquisitely sensitivity to androgen deprivation therapy.
There has been recent evidence that prostate cancer progression at the CRPC stage is still mediated by androgen receptor signaling, so it seems that subsequent androgen receptor targeting may further contribute to disease control and a survival benefit despite the seemingly resistance demonstrated.
Abiraterone acetate (Zytiga), which is a biosynthesis inhibitor of androgen receptor signaling, was evaluated in men with CRPC pretreated with docetaxel in a phase III trial. As theorized, the drug demonstrated an overall survival benefit, confirming that CRPC prostate cancer remains hormone driven, even in this very advanced stage.
The even better news is that there are several additional novel agents also targeting androgen receptor signaling in CRPC currently being evaluated. They include MDV3100 and TAK-700.
With the availability of newer endocrine treatments and the other non-endocrine treatments (e.g., chemotherapy, immunotherapy, and bone-targeting agents), data supporting a more rational use of therapeutic agents is urgently needed in men with CRPC.
Since there are currently great efforts to develop molecular characterizations of prostate cancer, it is likely that we will identify different subsets of prostate cancer with a different natural history, sensitivity, and resistance to treatment. This will require efforts to develop, validate, and implement predictive biomarkers in clinical trials and eventually in routine care of men with advanced prostate cancer.
Christophe Massard, Institut Gustave Roussy, Department of Cancer Medicine, University Paris Sud, Clin Cancer Res; 17(12); 3876–83. ©2011 AACR.
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