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MINI REVIEW article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1534055
This article is part of the Research Topic Renewed Insight into Cancer Mechanism and Therapy View all 10 articles

DNA Methylation and Immune Evasion in Triple-Negative Breast Cancer: Challenges and Therapeutic Opportunities

Provisionally accepted
Wen-yu Cai Wen-yu Cai 1Xin-Xian Cai Xin-Xian Cai 2*Yi-Ran Fei Yi-Ran Fei 3Rui Ye Rui Ye 2*Ding-ming Song Ding-ming Song 4Dan Hu Dan Hu 5*Wan- Wan Zhang Wan- Wan Zhang 1*Ming-Fei Xia Ming-Fei Xia 1*Xiao-Xiao Yang Xiao-Xiao Yang 1*
  • 1 The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine）, Hangzhou, China
  • 2 School of Medical Technology and lnformation Engineering, Zhejiang Chinese Medical University, Hangzhou, Jiangsu Province, China
  • 3 First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 4 First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China
  • 5 Cixi Integrated Traditional Chinese and Western Medicine Medical and Health Group, Cixi, China

The final, formatted version of the article will be published soon.

    Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Chemotherapy remains the primary treatment option, yet TNBC frequently develops resistance, leading to relapse and metastasis. Emerging evidence highlights the potential of combining DNA methylation inhibitors with immune checkpoint inhibitors (ICIs). DNA methylation contributes to immune escape by silencing immune-regulatory genes, thereby reducing the tumor's visibility to immune cells. Reversing this epigenetic modification can reinvigorate immune surveillance and enhance the efficacy of immunotherapies. This review discusses the role of DNA methylation in TNBC progression and immune evasion, focusing on recent advances in combination therapies involving DNA methylation inhibitors and ICIs. We discuss the underlying mechanisms that enable these therapeutic synergies, preclinical and clinical evidence supporting the approach, and the challenges posed by tumor heterogeneity, drug resistance, and toxicity. Finally, we explore the potential for personalized treatment strategies incorporating multi-omics data to optimize therapeutic outcomes. The integration of epigenetic therapies and immunotherapy offers a promising avenue for improving survival in TNBC patients.

    Keywords: Triple-negative breast cancer, DNA methylation inhibitors, immune checkpoint inhibitors, Immune Evasion, epigenetic therapy, personalized medicine

    Received: 25 Nov 2024; Accepted: 16 Jan 2025.

    Copyright: © 2025 Cai, Cai, Fei, Ye, Song, Hu, Zhang, Xia and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xin-Xian Cai, School of Medical Technology and lnformation Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, Jiangsu Province, China
    Rui Ye, School of Medical Technology and lnformation Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, Jiangsu Province, China
    Dan Hu, Cixi Integrated Traditional Chinese and Western Medicine Medical and Health Group, Cixi, 315300, China
    Wan- Wan Zhang, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine）, Hangzhou, China
    Ming-Fei Xia, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine）, Hangzhou, China
    Xiao-Xiao Yang, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine）, Hangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.