STAT3 and malignant glioma: As gain-of-function STAT3 mutations have not been described in GBM, aberrant STAT3 signaling in malignant glioma occurs predominantly as a result of dysregulated upstream events that ultimately promote proliferation; neovascularization; resistance to apoptosis; and immune escape through downstream targets, such as Bcl-xL, Bcl2l1, Bcl-2, cyclin D1, and c-Myc (Figure 2) [24,25].