In line with this, inhibition of canonical NOTCH1 pathways by the presence of gain-of-function mutations detected in some HNSCC patients, such as NOTCH1V1754L and NOTCH1C1133Y, can activate the EGFR-PI3K-AKT pathway (see also Section 3). The gene discussed is AKT1; the disease is head and neck squamous cell carcinoma.