Hyper-activation of the phosphatidylinositol3-kinase/PKB signaling pathway frequently observed in NB is associated with FOXO3-inactivation and its re-localization into the cytoplasm.4, 5, 11, 12, 13 However, in high-stage-derived NB cell lines FOXO3 partly localizes to the nucleus despite high PKB-activity and regulates the response to hypoxia within these cells (Figure 1).14 Activation by etoposide-treatment further increases the amount of nuclear FOXO3 (Figure 1c) suggesting that shuttling and oxidative stress response regulation of FOXO3 is still intact within these cells. Here, FOXO3 is linked to neuroblastoma.