The considerable heterogeneity of EGFR CNG and protein over-expression observed in ESCC may be a key determinant of resistance [16], with rapid selection and outgrowth occurring of EGFR CNG and protein overexpression-negative tumour cell sub-clones that are unresponsive to EGFR inhibitors. The gene discussed is EGFR; the disease is esophageal squamous cell carcinoma.