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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Authors | Stephan Wullschleger, Juan M García-Martínez, Suzanne L Duce |
Journal | Anticancer research
(Anticancer Res)
Vol. 32
Issue 2
Pg. 415-20
(Feb 2012)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 22287727
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
- Enzyme Inhibitors
- Indazoles
- Phosphoinositide-3 Kinase Inhibitors
- Sulfonamides
- PTEN Phosphohydrolase
- Pten protein, mouse
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Topics |
- Animals
- Cell Line, Tumor
- Disease Models, Animal
- Enzyme Inhibitors
(pharmacology)
- Female
- Head and Neck Neoplasms
(drug therapy, enzymology, pathology)
- Indazoles
(pharmacology)
- Longitudinal Studies
- Lymphoma, B-Cell
(drug therapy, enzymology, pathology)
- Lymphoma, Follicular
(drug therapy, enzymology, pathology)
- Magnetic Resonance Imaging
(methods)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- PTEN Phosphohydrolase
(deficiency)
- Phosphoinositide-3 Kinase Inhibitors
- Sulfonamides
(pharmacology)
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