NFKB1 and brain neoplasm: For malignant brain tumors, most of which exhibit aberrant PI3K activation, targeting the PI3K pathway and one or more of its downstream transcription factors, of which NFκB and CREB are emerging as potential small molecule inhibitor targets (Figure 1), will likely lead to a paradigm shift in therapy which will benefit patients who currently have limited treatment options and only short-term benefit.