APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response
The APOBEC (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like) family of cytidine deaminases has emerged as pivotal a contributor to genomic instability and adaptive immunity through DNA/RNA editing. Accumulating evidence underscores their dual role in breast carcinogenesis—driving tu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1604313/full |
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| author | Haiqi Lu Zelin Lu Yufei Wang Miaoqin Chen Guangliang Li Xian Wang |
| author_facet | Haiqi Lu Zelin Lu Yufei Wang Miaoqin Chen Guangliang Li Xian Wang |
| author_sort | Haiqi Lu |
| collection | DOAJ |
| description | The APOBEC (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like) family of cytidine deaminases has emerged as pivotal a contributor to genomic instability and adaptive immunity through DNA/RNA editing. Accumulating evidence underscores their dual role in breast carcinogenesis—driving tumor heterogeneity via mutagenesis while simultaneously shaping immunogenic landscapes. This review synthesizes current insights into APOBEC-mediated molecular mechanisms, focusing on their clinical implications across breast cancer subtypes. Notably, APOBEC-driven mutagenesis correlates with elevated tumor mutational burden (TMB), replication stress vulnerability, and immune checkpoint inhibitor (ICI) responsiveness. Paradoxically, these mutations also accelerate endocrine therapy resistance and subclonal diversification. We propose APOBEC mutational signatures as predictive biomarkers for ICI efficacy and discuss therapeutic strategies leveraging APOBEC activity, including ATR inhibition and hypermutagenic immunotherapy. Harnessing APOBEC’s duality—balancing its pro-immunogenic effects against genomic chaos—may redefine precision oncology in breast cancer. |
| format | Article |
| id | doaj-art-c1f0779bf934432cad16e135cbbc0ba2 |
| institution | OA Journals |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-c1f0779bf934432cad16e135cbbc0ba22025-08-20T02:29:00ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-04-011210.3389/fmolb.2025.16043131604313APOBEC in breast cancer: a dual player in tumor evolution and therapeutic responseHaiqi Lu0Zelin Lu1Yufei Wang2Miaoqin Chen3Guangliang Li4Xian Wang5Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaThe APOBEC (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like) family of cytidine deaminases has emerged as pivotal a contributor to genomic instability and adaptive immunity through DNA/RNA editing. Accumulating evidence underscores their dual role in breast carcinogenesis—driving tumor heterogeneity via mutagenesis while simultaneously shaping immunogenic landscapes. This review synthesizes current insights into APOBEC-mediated molecular mechanisms, focusing on their clinical implications across breast cancer subtypes. Notably, APOBEC-driven mutagenesis correlates with elevated tumor mutational burden (TMB), replication stress vulnerability, and immune checkpoint inhibitor (ICI) responsiveness. Paradoxically, these mutations also accelerate endocrine therapy resistance and subclonal diversification. We propose APOBEC mutational signatures as predictive biomarkers for ICI efficacy and discuss therapeutic strategies leveraging APOBEC activity, including ATR inhibition and hypermutagenic immunotherapy. Harnessing APOBEC’s duality—balancing its pro-immunogenic effects against genomic chaos—may redefine precision oncology in breast cancer.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1604313/fullAPOBEC mutagenesisbreast cancer subtypesimmune checkpoint blockadetumor mutational burdentherapeutic resistance |
| spellingShingle | Haiqi Lu Zelin Lu Yufei Wang Miaoqin Chen Guangliang Li Xian Wang APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response Frontiers in Molecular Biosciences APOBEC mutagenesis breast cancer subtypes immune checkpoint blockade tumor mutational burden therapeutic resistance |
| title | APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response |
| title_full | APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response |
| title_fullStr | APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response |
| title_full_unstemmed | APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response |
| title_short | APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response |
| title_sort | apobec in breast cancer a dual player in tumor evolution and therapeutic response |
| topic | APOBEC mutagenesis breast cancer subtypes immune checkpoint blockade tumor mutational burden therapeutic resistance |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1604313/full |
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