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Updated: Dec 23, 2025
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Reversal of HER2 Negativity: An Unexpected Role for Lovastatin in Triple-Negative Breast Cancer Stem Cells
Huimei Yi1,2, Mi Wu1,2, Qiuting Zhang1
1Key Laboratory of Translational Cancer Stem Cell Research, Hunan Normal University, Changsha, Hunan 410013, China.
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.
Insights
Lovastatin shows promise in treating triple-negative breast cancer (TNBC) by targeting cancer stem cells. Combining lovastatin with HER2 and EGFR inhibitors offers a potential synergistic therapy for TNBC.
Area of Science:
- Oncology
- Pharmacology
- Cancer Stem Cell Biology
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies due to absent receptor expression.
- Cancer stem cells (CSCs) are implicated in TNBC progression and treatment resistance.
- Lovastatin, a HMG-CoA reductase inhibitor, has shown selective inhibition of TNBC CSCs.
Purpose of the Study:
- To investigate lovastatin's mechanism in TNBC.
- To explore the potential of restoring receptor tyrosine kinase (RTK) sensitivity in TNBC CSCs.
- To evaluate combination therapies involving lovastatin and RTK inhibitors.
Main Methods:
- In vitro and in vivo studies using TNBC models.
- Treatment with lovastatin alone and in combination with HER2 and EGFR inhibitors.
- Assessment of cell viability and CSC targeting.
Main Results:
- Lovastatin selectively inhibited TNBC CSCs and induced HER2 expression.
- Combination of lovastatin with a HER2 inhibitor showed limited synergy.
- A triple combination of lovastatin, HER2 inhibitor, and EGFR inhibitor demonstrated significant synergistic inhibition of TNBC cell viability.
Conclusions:
- Lovastatin can re-sensitize TNBC CSCs to RTK-targeted therapies.
- A novel therapeutic strategy involving a lipid-lowering drug and dual RTK inhibitors is proposed for TNBC treatment.
- This combination therapy holds potential for overcoming treatment resistance in TNBC.
