While it is highly tempting to therapeutically inhibit PI3K/Akt (that is constitutively active in many cancers) driving the accumulation of nuclear FOXO [52], a recent, important study revealed that in the presence of high nuclear β-catenin, that the activation of FOXO3a by PI3K or Akt inhibitors induced metastasis rather than mediating a pro-apoptotic anti-tumor response as would have been predicted [53]. The gene discussed is AKT1; the disease is neoplasm.