DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities
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 resista...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1534055/full |
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| author | Wen-yu Cai Xin-xian Cai Yi-ran Fei Rui Ye Ding-ming Song Dan Hu Wan-wan Zhang Ming-fei Xia Xiao-xiao Yang |
| author_facet | Wen-yu Cai Xin-xian Cai Yi-ran Fei Rui Ye Ding-ming Song Dan Hu Wan-wan Zhang Ming-fei Xia Xiao-xiao Yang |
| author_sort | Wen-yu Cai |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-38d6a4b65f1648d081b31345585f88e1 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-38d6a4b65f1648d081b31345585f88e12025-02-06T05:21:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-02-011510.3389/fonc.2025.15340551534055DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunitiesWen-yu Cai0Xin-xian Cai1Yi-ran Fei2Rui Ye3Ding-ming Song4Dan Hu5Wan-wan Zhang6Ming-fei Xia7Xiao-xiao Yang8The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, ChinaThe First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Urology, Jinzhou Medical University, The First Hospital of Jinzhou Medical University, Jinzhou, Liaoning, ChinaDepartment of Clinical Lab, The Cixi Integrated Traditional Chinese and Western Medicine Medical and Health Group Cixi Red Cross Hospital, Cixi, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaTriple-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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1534055/fulltriple-negative breast cancerDNA methylation inhibitorsimmune checkpoint inhibitorsimmune evasionepigenetic therapypersonalized medicine |
| spellingShingle | Wen-yu Cai Xin-xian Cai Yi-ran Fei Rui Ye Ding-ming Song Dan Hu Wan-wan Zhang Ming-fei Xia Xiao-xiao Yang DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities Frontiers in Oncology triple-negative breast cancer DNA methylation inhibitors immune checkpoint inhibitors immune evasion epigenetic therapy personalized medicine |
| title | DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities |
| title_full | DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities |
| title_fullStr | DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities |
| title_full_unstemmed | DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities |
| title_short | DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities |
| title_sort | dna methylation and immune evasion in triple negative breast cancer challenges and therapeutic opportunities |
| topic | triple-negative breast cancer DNA methylation inhibitors immune checkpoint inhibitors immune evasion epigenetic therapy personalized medicine |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1534055/full |
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