title: Lessons from in-vivo models of castration-resistant prostate cancer.
abstract: OBJECTIVE
  Although the treatment of castration-resistant prostate cancer (CRPC) has benefited from the use of increasingly potent androgen synthesis inhibitors and androgen receptor (AR) antagonists, it is only marginally effective. There is therefore a critical need for a better understanding of the mechanisms underlying the CRPC development and more effective therapeutic approaches. Here, we focus on the advancements reported in the last 18 months, particularly with regard to the mechanisms of castration resistance and potential therapeutic targets emerging from the studies with in-vivo models.
  
  
  RESULTS
  Recent findings indicate that AR-dependent mechanisms, for example, increased expression of CYP17A1 and AR splice variants, play important roles in in-vivo castration resistance to new antiandrogens and androgen synthesis inhibitors. Whereas current therapeutic approaches focus on AR-dependent CRPC, studies based on genetically engineered mouse models indicate that castration resistance can develop in the absence of robust AR signaling. Furthermore, increasing evidence suggests that cellular plasticity of prostate adenocarcinoma allows AR-independent CRPC development via various adaptive mechanisms.
  
  
  CONCLUSIONS
  Significant progress has been made in the understanding of AR-dependent and AR-independent mechanisms involved in the development of CRPC. This may lead to identification of new therapeutic targets and improved therapy.
authors: The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors: Dong
authors: D
authors: Lin
authors: Peter W
authors: PW
authors: Gout
authors: Yuzhuo
authors: Y
authors: Wang
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008024:Ligands; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D008024:Ligands; D011944:Receptors, Androgen