A differential response in two HNSCC cell lines toward the PI3K-mTOR inhibitor, PF-04691502 was described by Tonlaar et al. While one strain was sensitized, the other failed to respond, in line with an increased constitutive activity of PI3K, AKT, and mTOR and an inability to inhibit key phosphorylation events upon treatment (74). This evidence concerns the gene AKT1 and head and neck squamous cell carcinoma.