title: Response of Degarelix treatment in human prostate cancer monitored by HR-MAS1H NMR spectroscopy.
abstract: BACKGROUND
  The androgen receptor (AR) is the master regulator of prostate cancer cell metabolism. Degarelix is a novel gonadotrophin-releasing hormone blocker, used to decrease serum androgen levels in order to treat advanced human prostate cancer. Little is known of the rapid metabolic response of the human prostate cancer tissue samples to the decreased androgen levels.
  
  
  OBJECTIVE
  To investigate the metabolic responses in benign and cancerous tissue samples from patients after treatment with Degarelix by using HRMAS1H NMR spectroscopy.
  
  
  METHODS
  Using non-destructive HR-MAS1H NMR spectroscopy we analysed the metabolic changes induced by decreased AR signalling in human prostate cancer tissue samples. Absolute concentrations of the metabolites alanine, lactate, glutamine, glutamate, citrate, choline compounds [t-choline = choline + phosphocholine (PC) + glycerophosphocholine (GPC)], creatine compounds [t-creatine = creatine (Cr) + phosphocreatine (PCr)], taurine, myo-inositol and polyamines were measured in benign prostate tissue samples (n = 10), in prostate cancer specimens from untreated patients (n = 7) and prostate cancer specimens from patients treated with Degarelix (n = 6).
  
  
  RESULTS
  Lactate, alanine and t-choline concentrations were significantly elevated in high-grade prostate cancer samples when compared to benign samples in untreated patients. Decreased androgen levels resulted in significant decreases of lactate and t-choline concentrations in human prostate cancer biopsies.
  
  
  CONCLUSIONS
  The reduced concentrations of lactate and t-choline metabolites due to Degarelix could in principle be monitored by in vivo1H MRS, which suggests that it would be possible to monitor the effects of physical or chemical castration in patients by that non-invasive method.
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
authors.forename: Basetti
authors.identifier: 0000-0001-5844-856X
authors.initials: B
authors.lastname: Madhu
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK ; Department of Urology, Cambridge University Hospitals NHS Trust, Cambridge, UK ; University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Greg L
authors.initials: GL
authors.lastname: Shaw
authors.affiliation: Department of Pathology, Cambridge University Hospitals NHS Trust, Cambridge, UK.
authors.forename: Anne Y
authors.initials: AY
authors.lastname: Warren
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK ; Department of Urology, Cambridge University Hospitals NHS Trust, Cambridge, UK ; Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Headington, Oxford, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Griffiths
keywords: Cancer; Degarelix; HR-MAS; Metabolism; Metabolomics; NMR; Prostate