Using, as examples, the PI3K pathway associated transcription factors, described in this review, one can envisage the rational development of novel brain cancer drug combinations comprising FDA-approved PI3K pathway drugs, such as everolimus and/or BKM120, which can cross the blood-brain barrier, and an ever-growing list of experimental inhibitors specifically targeting FOXO, NFκB, and CREB. Here, NFKB1 is linked to brain cancer.