Cholesterol synthesis disruption combined with a molecule-targeted drug is a promising metabolic therapy for EGFR mutant non-small cell lung cancer.

BACKGROUND

Acquired resistance is a challenge for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer. Here, we propose a novel treatment strategy based on recent lipid metabolism work.

METHODS

We applied a variety of experimental methods such as immunoblotting, MTT, si-RNA, and animal models, to demonstrate the relationship between EGFR and low-density lipoprotein receptor (LDLR) and the effects of statin monotherapy, and TKI monotherapy, and their combination on cell proliferation at the cell level and animal level.

RESULTS

LDLR has a positive correlation with EGFR, EGFR signaling upregulates LDLR expression through the SREBP-1 dependent pathway, EGFR mutation cells count on lipids to survive and grow. Combined with a molecule-targeted drug, atorvastatin not only enhances the treatment effect , but also mitigates the growth of NSCLC . In this animal experiment, the combination medicine (atorvastatin with TKI) has a better tumor suppression effect on NSCLC. In HCC827 cell line, the average tumor shrinkage is about 68% in Gefitinib group, and about 49% in atorvastatin group, but about 89% in combination group. In H1975 cell line, the average tumor shrinkage is about 18% in Osimertinib group, and about 8% in atorvastatin group, but about 44% in combination group.

CONCLUSIONS

the combination of an EGFR-TKI and a statin for EGFR mutant NSCLC may be a novel tumor inhibiting treatment.