Fig. 4.

In vivo effects of PI3K and mitogen-activated protein kinase (MEK) inhibition. Quantification of pre- and posttreatment luciferase signal over time for subcutaneous xenograft experiments (A). Posttreatment time points were analyzed with two-way analysis of variance, with no significant difference between treatment groups (F(3,14) = 1.69, P = .21). Error bars SD. Kaplan–Meier curve of genetically engineered mouse model (GEMM) treated with either vehicle or combination of ZSTK474 and trametinib (B). Median survival time was 47 days for vehicle group versus 35 days for treatment group, log rank P = .038. Tumor histology from the intracranial GEMM showing features typical of diffuse intrinsic pontine glioma (DIPG), including markedly atypical cells with irregularly contoured nuclei, high cellular density, palisading necrosis, and infiltration of tumor cells into surrounding brain tissue. Scale bars as 1 mm and 125 µm, as indicated. (C).