Journal
JOURNAL OF CANCER
Volume 11, Issue 13, Pages 3713-3716Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.39265
Keywords
triple-negative breast cancer; reversal; HER2; cancer stem cell; cancer therapy; lovastatin
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Funding
- Natural Science Foundation of China [81872167, 81472496]
- Natural Science Foundation of Hunan [2019JJ40193]
- Hunan Provincial Innovation Foundation for Postgraduate [CX2018B305]
- Key Project of Department of Education of Hunan Province [14A089]
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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.
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