J Cancer 2020; 11(13):3713-3716. doi:10.7150/jca.39265 This issue
Short Research Paper
1. Key Laboratory of Translational Cancer Stem Cell Research, Hunan Normal University, Changsha, Hunan 410013, China;
2. Departments of Pathology and Pathophysiology, Hunan Normal University School of Medicine, Changsha, Hunan 410013, China.
*These authors contributed equally to this work.
Effective treatment modality for triple-negative breast cancer (TNBC) is currently lacking due to the absence of defined receptor targets. Recently, we have demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor and a lipid-lowering drug, can selectively inhibit TNBC by targeting cancer stem cells in vivo and in vitro. Interestingly, we found that lovastatin induced the reappearance of human epidermal growth factor receptor 2 (HER2), one of the triple receptors that are missing in TNBC. This prompted us to explore the possibility of regaining sensitivity of TNBC cancer stem cells to receptor tyrosine kinase-targeting drugs. We found that while the combination of lovastatin with a HER2 inhibitor was not sufficient to show synergism, addition of an epidermal growth factor receptor (EGFR/HER1) inhibitor to this combination resulted in significant synergistic inhibitory effect on cell viability. Our findings provide a potential novel strategy of designing a cocktail composed of a lipid-lowering drug and two receptor tyrosine kinase inhibitors for the treatment of TNBC.
Keywords: triple-negative breast cancer, reversal, HER2, cancer stem cell, cancer therapy, lovastatin