Efforts to unravel the molecular pathogenesis of HNSCC through The Cancer Genome Atlas Project (TCGA) and other large scale genomic and transcriptomic analyses have identified a significant number of potentially actionable targets (e.g., PI3K, NOTCH1, TRAF3), although there remains a dearth of effective therapies [19, 34]. Here, NOTCH1 is linked to head and neck squamous cell carcinoma.