title: Phase I and II therapies targeting the androgen receptor for the treatment of castration resistant prostate cancer.
abstract: BACKGROUND
  Prostate cancer is the most common cancer in elderly males. Regardless of the initial hormonal treatment in metastatic disease, a significant proportion of patients develop castration resistant prostate cancer (CRPC). A better understanding of the molecular mechanisms behind castration resistance has led to the approval of oral medications such as abiraterone acetate and enzalutamide. Relevant research is accelerated with numerous agents being tested for the management of CRPC.
  
  
  METHODS
  The authors present Phase I and II studies targeting the androgen receptor for the treatment of CRPC. Three groups of agents are identified according to the mechanism of action. These include the CYP-17 modulators (Orteronel, Galeterone, VT-464 and CFG-920), novel antiandrogens (Apatorsen, ARN-509, ODM-201, EZN-4176, AZD-3514) and bipolar androgen therapy.
  
  
  CONCLUSIONS
  Further understanding of the mechanisms leading to castration resistance in prostate cancer can reveal potential targets for the development of novel anti-cancer agents. Except for the development of novel antiandrogens and CYP-17 modulators, bipolar androgen therapy is an interesting therapeutic approach. The combinations of the novel agents tested in Phase I and II studies with established agents is another field of interest. The real challenge is to distinguish a novel anti-cancer agent with acceptable tolerability and the best outcome.
authors.affiliation: a University Department of Urology , Sismanoglio Hospital , Athens , Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Dellis
authors.affiliation: a University Department of Urology , Sismanoglio Hospital , Athens , Greece.|b Department of Urology, Addenbrooke's Hospital , Cambridge University Hospitals NHS , Cambridge , UK.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papatsoris
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D059002:Androgen Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D013254:Steroid 17-alpha-Hydroxylase / Q000187:drug effects / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D013254:Steroid 17-alpha-Hydroxylase
keywords: CYP-17; Prostate; androgen receptor; antiandrogens; bipolar androgen therapy; cancer; castration resistance