ERBB2 and esophageal squamous cell carcinoma: IGF-1R was found to be compensated by activation after the EGFR/HER2 signaling pathway was inhibited, so the efficacy of receptor TKIs alone was not significant, while the combination of the dual EGFR/HER2 inhibitors lapatinib and gefitinib with the IGF-1R inhibitor linsitinib, inhibited the mutual crosstalk between EGFR/HER2 and IGF-1R, remarkably enhancing ESCC cell cycle arrest and apoptosis [113].