title: Quantitative MRI establishes the efficacy of PI3K inhibitor (GDC-0941) multi-treatments in PTEN-deficient mice lymphoma.
abstract: OBJECTIVE
  To assess the efficacy of multiple treatment of phosphatidylinositol-3-kinase (PI3K) inhibitor on autochthonous tumours in phosphatase and tensin homologue (Pten)-deficient genetically engineered mouse cancer models using a longitudinal magnetic resonance imaging (MRI) protocol.
  
  
  METHODS
  Using 3D MRI, B-cell follicular lymphoma growth was quantified in a Pten(+/-)Lkb1(+/hypo) mouse line, before, during and after repeated treatments with a PI3K inhibitor GDC-0941 (75 mg/kg).
  
  
  RESULTS
  Mean pre-treatment linear tumour growth rate was 16.5±12.8 mm(3)/week. Repeated 28-day GDC-0941 administration, with 21 days 'off-treatment', induced average tumour regression of 41±7%. Upon cessation of the second treatment (which was not permanently cytocidal), tumours re-grew with an average linear growth rate of 40.1±15.5 mm(3)/week. There was no evidence of chemoresistance.
  
  
  CONCLUSIONS
  This protocol can accommodate complex dosing schedules, as well as combine different cancer therapies. It reduces biological variability problems and resulted in a 10-fold reduction in mouse numbers compared with terminal assessment methods. It is ideal for preclinical efficacy studies and for phenotyping molecularly characterized mouse models when investigating gene function.
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Stephan
authors.initials: S
authors.lastname: Wullschleger
authors.forename: Juan M
authors.initials: JM
authors.lastname: García-Martínez
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Duce
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D007191:Indazoles / Q000494:pharmacology*; D008137:Longitudinal Studies; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C532162:2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine; D004791:Enzyme Inhibitors; D007191:Indazoles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013449:Sulfonamides; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse