In GBM cell lines and mouse models, COX-2-derived PGE2 promotes glioma stem cells (GSC) self-renewal and therapy resistance through the EP4 receptor that activates the MAPK signaling cascade, leading to the up-regulation of the inhibitor of differentiation 1 (Id1), a main mediator that abrogates differentiation signals in GSC and contributes to chemoresistance in GBM. This evidence concerns the gene ID1 and central nervous system cancer.