Alteration of DNA methyltransferases by eribulin elicits broad DNA methylation changes with potential therapeutic implications for triple-negative breast cancer.

IF 3 4区医学 Q2 GENETICS & HEREDITY

Epigenomics Pub Date : 2024-03-01 Epub Date: 2024-02-15 DOI:10.2217/epi-2023-0339

Meisam Bagheri, Min Kyung Lee, Kristen E Muller, Todd W Miller, Diwakar R Pattabiraman, Brock C Christensen

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引用次数: 0

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.

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艾瑞布林对DNA甲基转移酶的改变引起了广泛的DNA甲基化变化，对三阴性乳腺癌具有潜在的治疗意义。

背景：三阴性乳腺癌（TNBC三阴性乳腺癌（TNBC）是一种侵袭性疾病，治疗方案有限。艾瑞布林是一种化疗药物，它能诱导癌细胞发生表观遗传学变化，这表明艾瑞布林具有独特的作用机制。材料与方法用艾瑞布林和紫杉醇处理MDA-MB 231细胞，用免疫组化方法比较53例接受新辅助艾瑞布林治疗的患者样本和14例接受标准治疗的患者样本。结果显示艾瑞布林治疗可引起耐药TNBC顽固细胞DNA甲基化的显著变化，还可引起体外和原发性TNBC肿瘤中表观遗传修饰因子（DNMT1、TET1、DNMT3A/B）表达水平的变化。结论这些发现为了解艾瑞布林的作用机制和预测TNBC治疗反应的潜在生物标志物提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Epigenomics GENETICS & HEREDITY-

CiteScore

5.80

自引率

2.60%

发文量

审稿时长

>12 weeks

期刊介绍： Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community. Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.