Alteration of DNA methyltransferases by eribulin elicits broad DNA methylation changes with potential therapeutic implications for triple-negative breast cancer.
Meisam BagheriMin Kyung LeeKristen E MullerW Todd MillerDiwakar R PattabiramanBrock C ChristensenPublished in: Epigenomics (2024)
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.
Keyphrases
- dna methylation
- metastatic breast cancer
- genome wide
- phase ii
- gene expression
- induced apoptosis
- cell cycle arrest
- healthcare
- clinical trial
- poor prognosis
- cell death
- randomized controlled trial
- copy number
- rectal cancer
- lymph node
- radiation therapy
- cell proliferation
- pain management
- replacement therapy
- drug induced
- breast cancer cells
- binding protein
- smoking cessation
- phase iii
- double blind
- nucleic acid
- newly diagnosed