Xenograft Tumor Models for GIST and NSCLC

Female CB.17 (SCID) mice (Charles River Laboratories, Wilmington, MA) at 7–12 weeks of age were maintained in a pathogen-free environment and all in vivo procedures were approved by the Synta Pharmaceuticals Corp. Institutional Animal Care and Use Committee. Human GIST882 cells were provided by Dr. Jonathan Fletcher (Dana Farber Cancer Institute) and implanted subcutaneously at 10 × 10⁶ into mice. Mice bearing established tumors (~110 mm³) were randomized into treatment groups of 8 and dosed intravenously with vehicle or ganetespib, formulated in DRD (10% DMSO, 18% Cremophor RH 40, 3.6% dextrose), using the schedules indicated. Human H1975 NSCLC cells were purchased from the ATCC, selected to stably express a HIF-1α-LUC reporter and implanted at 10 × 10⁶ into mice. Mice bearing established tumors (~143 mm³) were randomized into treatment groups of 4 and dosed intravenously with vehicle or ganetespib, formulated in DRD, using the schedules indicated. Tumor volumes (V) were calculated by caliper measurements of the width (W), length (L) and thickness (T) of each tumor using the formula: V=0.5236(LWT). Tumor growth inhibition was determined as described previously (16 (link)). Statistical analyses were conducted using two-way ANOVA followed by Bonferroni post tests.