A variant of EFGR (EGFRvIII) that results in constitutive activation of the downstream Ras/Raf/MAPK, STAT3 and PI3/AKT/mTOR pathways has been observed in HNSCC that is not responsive to EGFR inhibition [204]. The gene discussed is AKT1; the disease is head and neck squamous cell carcinoma.