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

Abstract

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.

• Authors: Huimei Yi, Mi Wu, Qiuting Zhang, Lu Lu, Hui Yao, Sisi Chen, Ying Li, Chanjuan Zheng, Guangchun He, Xiyun Deng
• Journal: Journal of Cancer (J Cancer) Vol. 11 Issue 13 Pg. 3713-3716 ( 2020) ISSN: 1837-9664 [Print] Australia
• PMID: 32328175 (Publication Type: Journal Article)
• Copyright: © The author(s).