STAT3 and head and neck squamous cell carcinoma: Although EGFR activation has been found to lead to the rapid phosphorylation of STAT3 on tyrosine 705 and the subsequent activation of STAT3-dependent gene expression, STAT3 tyrosine phosphorylation and the formation of active STAT3 DNA-binding complexes were insensitive to EGFR inhibition in many HNSCC cell lines [59].