1,25(OH)2D3 restores sensitivity to EGFR TKIs in EMT-associated models of acquired resistance to EGFR targeted therapies. (A) H1975, SH416, and PC9 cells and the corresponding TKI-resistant sublines were treated with vehicle control, 1 µM erlotinib (SH416/SH416ER and PC9/PC9–ER) or 0.5 µM osimertinib (H1975/H1975–OR), 100 nM 1,25(OH)2D3, or combination of the above agents every 72 h for a total of 9 days. The number of surviving cells at day 9 in each treatment group was normalized to that in the vehicle control group. * p < 0.05; **** p < 0.0001. (B) H1975–OR and SH416–ER cells were treated with increasing concentrations of the corresponding EGFR TKIs alone or in combination with 1,25(OH)2D3 every 72 h for a total of 9 days. All experiments were performed in triplicates.