AI Article Synopsis
- The study aimed to evaluate how effective the PI3K inhibitor GDC-0941 is in treating tumors in specific genetically engineered mouse models lacking the Pten gene, using advanced MRI techniques for monitoring.
- The research showed that after a 28-day treatment regimen with GDC-0941, there was a significant average tumor size reduction of 41%, although tumors started regrowing rapidly once treatment ended, with no signs of chemoresistance observed.
- This treatment and monitoring approach allows for flexible dosing schedules, minimizes biological variation, and significantly reduces the number of mice needed for testing compared to traditional methods, making it suitable for preclinical cancer research.
Article 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 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.
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.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292793 | PMC |
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