UPF1 and neoplasm: 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.