There are hints that constitutive activation of PI3K–AKT signaling could be exploited therapeutically because it underlies a differential stress response between malign and benign cells, such that only the latter increase their resistance against cytotoxic insults upon reduction of growth factors induced by CR.70 In C57BL/6J mice, CR promoted stress resistance in a FOXO1-dependent manner,71 which would not occur in tumor cells with FOXO inactivation due to constitutively active AKT. The gene discussed is PIK3CA; the disease is neoplasm.