Furthermore, the modulation of XAF1 expression in MGMT-hyper GBM during evolution towards adaptive resistance, in conjunction with the observation that XAF1 expression negatively correlates with longterm survival in GBM (Fig. 1e), support our hypothesis that XAF1 might have an aggressive role in GBM that is paradoxical to its role as a tumor suppressor in other cancers. This evidence concerns the gene XAF1 and cancer.