As expected, the combination of alpelisib and trametinib was very potent against all three HNSCC cell lines (Fig. 3A and B) with alpelisib blocking and some TORC1 signaling in all three lines, trametinib blocking MEK signaling in all three lines, and the combination of the two robustly blocking mTORC1 signaling (Fig. 3C and D) in all three lines, consistent with our past work (38, 42) and others (15, 43). The gene discussed is CRTC1; the disease is head and neck squamous cell carcinoma.