Abstract 1212: Effect of metformin and insulin-/IGF1-receptor inhibitor combination drug therapy in triple negative breast cancer

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor survival outcomes. Chemotherapy is the only approved treatment, as there are no targeted therapies. Metformin is an anti-diabetic drug for Type 2 Diabetes. It has been shown to have anti-tumor effects by lowering serum levels of the mitogen insulin, and by pleiotropic effects on cancer cell signaling pathways. BMS-754807 is a potent and reversible inhibitor of the insulin receptor (IR)/insulin-like growth factor 1 receptor (IGF-1R) family kinases that has been shown to have activity in a subset of TNBC. The aim of this study is to evaluate the hypothesis that the combination of metformin and BMS-754807 is more effective than single drug treatment in TNBC.

Experimental design and methods: We treated TNBC cell lines with metformin and BMS-754807 alone and in combination and tested cell viability using MTS assays. Then we used CompuSyn software to analyze the dose-effect of drug combinations for additivity, synergism, or antagonism. We also examined the mechanism by performing Western blots of candidate pathways.

Results: 5 out of the 9 cell lines tested (56%) showed synergism of metformin and BMS-754807 in the drug combination assays. Western blots showed significant inhibition of IR/IGF-1R and PI3K/Akt pathways with the drug combination.

Conclusion: We conclude that the combination of metformin and BMS-754807 is more effective than single drug in a significant proportion of triple negative breast cancer cell lines. This combination may represent effective targeted therapy for a subset of TNBC. Further studies to evaluate this possibility are underway.

Citation Format: Lei Xue, Laura Camacho, Sushma Kothapalli, Sao Jiralerspong. Effect of metformin and insulin-/IGF1-receptor inhibitor combination drug therapy in triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1212.