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Updated: Jun 22, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Epigenetic Therapies in Triple-Negative Breast Cancer: Concepts, Visions, and Challenges
1Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Abstract:
Breast cancer, the most frequent malignancy in women worldwide, is a molecularly and clinically very heterogeneous disease. Triple-negative breast cancer is defined by the absence of hormone receptor and growth factor receptor ERBB2/HER2 expression. It is characterized by a more aggressive course of disease and a shortage of effective therapeutic approaches. Hallmarks of cancer cells are not only genetic alterations, but also epigenetic aberrations. The most studied and best understood alterations are methylation of the DNA base cytosine and the covalent modification of histone proteins. The reversibility of these covalent modifications make them attractive targets for therapeutic intervention, as documented in numerous ongoing clinical trials. Epidrugs, targeting DNA methylation and histone modifications, might offer attractive new options in treating triple-negative breast cancer. Currently, the most promising options are combination therapies in which the epidrug increases the efficiency of immuncheckpoint inhibitors. This review focusses exclusively on DNA methylation and histone modifications. In reviewing the knowledge about epigenetic therapies in breast cancer, and especially triple-negative breast cancer, the focus is on explaining concepts and raising awareness of what is not yet known and what has to be clarified in the future.
Insights
Epigenetic drugs targeting DNA methylation and histone modifications show promise for treating aggressive triple-negative breast cancer. Combination therapies, particularly with immune checkpoint inhibitors, are emerging as a key therapeutic strategy.
Area of Science:
- Oncology
- Epigenetics
- Cancer Biology
Background:
- Breast cancer is a heterogeneous malignancy with triple-negative breast cancer (TNBC) presenting a more aggressive course and limited treatment options.
- Cancer cells exhibit genetic and epigenetic aberrations, including DNA methylation and histone modifications.
- Epigenetic modifications are reversible, making them attractive targets for therapeutic intervention.
Purpose of the Study:
- To review current knowledge on epigenetic therapies for breast cancer, with a specific focus on triple-negative breast cancer.
- To explain concepts related to DNA methylation and histone modifications in TNBC.
- To highlight areas requiring future research and clarification in epigenetic treatment strategies for TNBC.
Main Methods:
- Review of existing literature on epigenetic modifications and therapies in breast cancer.
- Focus on DNA methylation and histone modifications as key epigenetic aberrations.
- Analysis of current clinical trials and combination therapy approaches.
Main Results:
- Epigenetic drugs targeting DNA methylation and histone modifications offer potential new therapeutic avenues for TNBC.
- Combination therapies, especially those combining epigenetic drugs with immune checkpoint inhibitors, demonstrate promising efficacy.
- Significant knowledge gaps and areas for future research exist in the field of epigenetic therapies for TNBC.
Conclusions:
- Epigenetic therapies, particularly targeting DNA methylation and histone modifications, represent a promising frontier for treating triple-negative breast cancer.
- Combination strategies, notably with immune checkpoint inhibitors, are crucial for enhancing treatment effectiveness.
- Further research is essential to fully elucidate the potential and optimize the application of epigenetic drugs in TNBC treatment.
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