FOXO3 and central nervous system cancer: Intriguingly, Brucker et al. [202] have shown that FOXO3a expression is positively correlated with glioma WHO grade in peri-necrotic tumor lesions (where there is higher cellular stress) and under hypoxic conditions independent of HIF-1α, its upregulation causes cell death in GBM LNT-229 cells in a caspase-independent manner.