title: Castration-resistant prostate cancer: novel therapeutics pre- or post- taxane administration.
abstract: 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.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. shiota@uro.med.kyushu-u.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.forename: Naohiro
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kuruma
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011944:Receptors, Androgen / Q000737:chemistry* / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D059002:Androgen Receptor Antagonists; D001952:Bridged-Ring Compounds; D011944:Receptors, Androgen; D043823:Taxoids; C080625:taxane