Vitamin D3 Metabolites Demonstrate Prognostic Value in EGFR-Mutant Lung Adenocarcinoma and Can be Deployed to Oppose Acquired Therapeutic Resistance

EGFR tyrosine kinase inhibitors (EGFR TKIs) are the standard of care treatment for patients with EGFR-mutant lung adenocarcinoma (LUAD). Although initially effective, EGFR TKIs are not curative. Disease inevitably relapses due to acquired drug resistance. Here, we tested the ability of 1,25(OH)2D3 to promote epithelial differentiation and restore EGFR TKI sensitivity in models of EGFR TKI resistance that were associated with epithelial–mesenchymal transition (EMT). RNA was isolated from 3 separate passages of H1975 and H1975–OR (osimertinib resistant) cells treated with either vehicle control, 500nM osimertinib, 100 nM 1,25(OH)2D3, or combination of the above agents for 96 h with treatments administered at t0, 48, and 92 h.