Although the Akt1-E17K mutation occurs in human cancer with only low frequency, our findings are of importance as they help to unravel the role of a cancer cell-specific mutation in the cellular radiation response and to understand the results of clinical studies testing the use of PI3K/Akt pathway inhibitors with distinct mechanisms of action in combination with chemotherapy or radiotherapy to overcome Akt1-mediated therapy resistance. This evidence concerns the gene AKT1 and cancer.