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Updated: Jul 3, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Alteration of DNA methyltransferases by eribulin elicits broad DNA methylation changes with potential therapeutic
Meisam Bagheri1,2, Min Kyung Lee3, Kristen E Muller2,4
1Department of Molecular & Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Abstract:
Background: Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options. Eribulin, a chemotherapeutic drug, induces epigenetic changes in cancer cells, suggesting a unique mechanism of action. Materials & methods: MDA-MB 231 cells were treated with eribulin and paclitaxel, and the samples from 53 patients treated with neoadjuvant eribulin were compared with those from 14 patients who received the standard-of-care treatment using immunohistochemistry. Results: Eribulin treatment caused significant DNA methylation changes in drug-tolerant persister TNBC cells, and it also elicited changes in the expression levels of epigenetic modifiers (DNMT1, TET1, DNMT3A/B) in vitro and in primary TNBC tumors. Conclusion: These findings provide new insights into eribulin's mechanism of action and potential biomarkers for predicting TNBC treatment response.
Insights
Eribulin alters DNA methylation and epigenetic modifiers in triple-negative breast cancer (TNBC) cells, offering new therapeutic strategies. This research highlights eribulin
Area of Science:
- Oncology
- Pharmacology
- Epigenetics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Eribulin, a chemotherapy agent, exhibits potential unique mechanisms of action through epigenetic modifications.
Purpose of the Study:
- To investigate the epigenetic effects of eribulin in TNBC.
- To identify potential biomarkers for predicting treatment response to eribulin.
Main Methods:
- Treatment of MDA-MB 231 cells with eribulin and paclitaxel.
- Immunohistochemical analysis of patient samples from eribulin-treated and standard-of-care groups.
- Assessment of DNA methylation and expression of epigenetic modifiers (DNMT1, TET1, DNMT3A/B).
Main Results:
- Eribulin induced significant DNA methylation changes in drug-tolerant persister TNBC cells.
- Eribulin altered the expression of epigenetic modifiers both in vitro and in primary TNBC tumors.
- Distinct epigenetic profiles were observed between eribulin-treated and standard-of-care groups.
Conclusions:
- Eribulin's mechanism of action involves significant epigenetic alterations in TNBC.
- Epigenetic modifiers may serve as predictive biomarkers for eribulin efficacy in TNBC treatment.
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