SMG1 is considered to be the main kinase that initiates the activation of NMD; however, a recent study indicates that the oncogenic AKT kinase can supplant the action of SMG1 [61, 62] complicating the therapeutic landscape and indicating that, depending on tumor type, the inhibition might be better applied on other upstream factors of the NMD pathway such as UPF1 or UPF2. This evidence concerns the gene UPF2 and neoplasm.