5-Fu is one of the widely used chemotherapeutic drug for the treatment of several types of solid tumours including ESCC.3 However, detrimental side effects and chemoresistance have limited effects of 5-Fu.3, 11 Intriguingly, treatment of Eca109 and KYSE150 cells with 5-Fu resulted in elevated level of pErk and pAkt (Figure 4a), which could be reversed by combination of melatonin (Figures 4b and c). This evidence concerns the gene EIF2AK3 and esophageal squamous cell carcinoma.