Figure 6.

Combined PI3-Kinase Inhibition with MEK Inhibition Induces Tumor Regression

(A) Waterfall plot showing tumor response in 10-week-old mice that were treated with tamoxifen for 2 weeks, left untreated for 5 days, and then treated with trametinib for 4 weeks. Each bar represents one tumor and response is shown relative to initial tumor volume before tamoxifen treatment.

(B) Representative histological images of lungs from mice, histological quantifications of tumor burden, and tumor number in mice treated as described in (A) are shown.

(C) Kras^LA2 mice were treated with GDC0941 (100 mg/kg/day; green bars), BYL719 (50 mg/kg/day; purple bars), trametinib (3 mg/kg/day; blue bars), the combination of GDC0941 or BYL719 with trametinib (full dose for each drug; red and yellow bars, respectively), or vehicle alone (black bars). The waterfall plot represents response on tumor growth after 4 weeks treatment. Each bar represents one tumor and response is shown relative to initial tumor volume before tamoxifen treatment. Representative images of lungs from mice on each treatment are also shown.

(D) H&E staining, tumor burden representation, and tumor number assessment from lungs treated with the drugs described in (C).

Error bars indicate mean ± SEM (significance using Student’s t test: ^∗p < 0.05 ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001). See also Figure S5.