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

TY - JOUR

T1 - Quantitative MRI establishes the efficacy of PI3K inhibitor (GDC-0941) multi-treatments in PTEN-deficient mice lymphoma

AU - Wullschleger, Stephan

AU - García-Martínez, Juan M.

AU - Duce, Suzanne L.

PY - 2012/2/1

Y1 - 2012/2/1

N2 - 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.

AB - 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.

KW - Drug resistance

KW - Follicular lymphoma

KW - GDC-0941

KW - Mouse cancer model

KW - MRI

KW - PI3k inhibitor

KW - PTEN

UR - https://www.scopus.com/pages/publications/84856851338

M3 - Article

C2 - 22287727

AN - SCOPUS:84856851338

SN - 0250-7005

VL - 32

SP - 415

EP - 420

JO - Anticancer Research

JF - Anticancer Research

IS - 2

ER -