In conclusion, our results suggest that an increased production of glycosylceramides contributes to the survival of clones resistant to osimertinib through the inhibition of apoptotic cell death, and the use of a GCS inhibitor may represent a promising strategy to treat EGFR-mutant NSCLC patients who have progressed to osimertinib, regardless of the mechanism of resistance. This evidence concerns the gene EGFR and non-small cell lung carcinoma.