Castration-resistant prostate cancer: from new pathophysiology to new treatment targets.
BACKGROUND
Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited.


OBJECTIVE
To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC.


METHODS
Novel targeted therapies in clinical trials were identified from registries. The MEDLINE database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies.


RESULTS
Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression has translated into a variety of treatment approaches. Agents targeting androgen receptor (AR) activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK-ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase 3 trials for patients with CRPC.


CONCLUSIONS
A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future.
Chi
Kim N
KN
BC Cancer Agency, Vancouver, British Columbia, Canada. kchi@bccancer.bc.ca
Bjartell
Anders
A
Dearnaley
David
D
Saad
Fred
F
Schröder
Fritz H
FH
Sternberg
Cora
C
Tombal
Bertrand
B
Visakorpi
Tapio
T
D000726:Androgen Antagonists / Q000627:therapeutic use; D059002:Androgen Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000502:physiology; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D011944:Receptors, Androgen / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D017211:Treatment Failure; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D019332:Endothelin-1; D018832:Molecular Chaperones; D011944:Receptors, Androgen; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor