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.

Epigenomics
|February 15, 2024
PubMed

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.

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.6K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.0K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K