Prexasertib, a CHK1/2 inhibitor, was demonstrated to reduce in vitro survival fraction of HNSCC cell lines combined with cisplatin, with or without RT, mainly through the downregulation of NOTCH signaling target genes (NOTCH1, NOTCH2, and NOTCH3) and their associated ligands (JAG1, JAG2, SKP2, MAML2, and DLL1). This evidence concerns the gene NOTCH2 and head and neck squamous cell carcinoma.