Quantitative MRI establishes the efficacy of PI3K inhibitor (GDC-0941) multi-treatments in PTEN-deficient mice lymphoma

Stephan Wullschleger, Juan M. García-Martínez, Suzanne L. Duce (Lead / Corresponding author)

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aim: 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. Materials and 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 165±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. Conclusion: 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.

Original languageEnglish
Pages (from-to)415-420
Number of pages6
JournalAnticancer Research
Volume32
Issue number2
Publication statusPublished - 1 Feb 2012

Keywords

  • Drug resistance
  • Follicular lymphoma
  • GDC-0941
  • Mouse cancer model
  • MRI
  • PI3k inhibitor
  • PTEN

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