Exogenous IGFBP3 reduced basal pIGF1R and pAKT, confirming that AKT is activated downstream of IGF1R in gefitinib-resistant ESCC, and rescued inhibition of pAKT (Fig. 4d) and significantly resensitised TE11iresR#3 cells to gefitinib (Fig. 4e, f). Here, IGFBP3 is linked to esophageal squamous cell carcinoma.