In addition to MDR, the deregulation of DNA repair signaling pathways, anti-apoptotic proteins (Bcl2, Bcl-xL, survivin, BMI), and tyrosine kinases (EGFR, cMET), also promote resistance to these DNA damaging agents.168 In addition to these acquired mechanisms, a growing body of evidence suggests that tumor-initiating cells (TICs) or CSCs are intrinsically resistant to standard CRT.169,170 All these mechanisms have been known for decades in HNSCC, but issues related to the resistance mechanism to IT have been gradually emphasized recently. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.