J Cancer 2020; 11(13):3713-3716. doi:10.7150/jca.39265 This issue

Short Research Paper

Reversal of HER2 Negativity: An Unexpected Role for Lovastatin in Triple-Negative Breast Cancer Stem Cells

Huimei Yi1,2*, Mi Wu1,2*, Qiuting Zhang1, Lu Lu1,2, Hui Yao1,2, Sisi Chen1,2, Ying Li1,2, Chanjuan Zheng1, Guangchun He1,2, Xiyun Deng1,2✉

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.

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Yi H, Wu M, Zhang Q, Lu L, Yao H, Chen S, Li Y, Zheng C, He G, Deng X. Reversal of HER2 Negativity: An Unexpected Role for Lovastatin in Triple-Negative Breast Cancer Stem Cells. J Cancer 2020; 11(13):3713-3716. doi:10.7150/jca.39265. Available from https://www.jcancer.org/v11p3713.htm

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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