Castration-resistant Prostate Cancer: Novel Therapeutics Pre- or Post- Taxane Administration
Until 2010 docetaxel was the only agent with a proven survival benefit in the treatment of castration-resistant
prostate cancer (CRPC). Recent evidence suggests that CRPC is caused by augmented androgen/androgen receptor (AR)
signaling involving AR hypersensitivity, promiscuous activation of the AR, de novo production of androgens and
activation of the AR by cytokines and growth factors; these findings have led to the development of novel agents targeting
AR signaling. Several novel drugs targeting the AR axis, including the cytochrome P17 inhibitor abiraterone acetate and
anti-androgen enzalutamide (MDV3100), have shown promising results in prolonging survival in clinical trials in a postchemotherapy
setting. Because of these encouraging findings, these drugs have also been evaluated in a pre-chemotherapy
setting. In addition, several novel drugs targeting non-AR signaling, including the novel taxoid compound cabazitaxel,
antisense oligonucleotide OGX-011 (custirsen), sipuleucel-T immunotherapy and Alpharadin-based radiotherapy, have
also been demonstrated to improve overall survival in CRPC. However, there is no consensus with regard to the sequence
in which these novel drugs and taxanes should be used in the treatment of CRPC. In this review, we summarize recently
developed and developing novel agents for use against CRPC. We also discuss the sequence of use of these agents and
taxanes, mainly from the standpoint of factors related to drug resistance.
Keywords: Androgen receptor, castration-resistant prostate cancer, docetaxel, prostate cancer.
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