Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastoma
Neuroblastoma (NB), the most prevalent extracranial solid malignancy in children, poses significant therapeutic challenges, particularly concerning high-risk subtypes characterized by an immunologically “cold” phenotype. These tumors evade immune surveillance through mechanisms such as impaired anti...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1637626/full |
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| author | Xiaokang Wang Gengrui Xu Hongyan Ma Xiaoyan Deng Guiping Ma |
| author_facet | Xiaokang Wang Gengrui Xu Hongyan Ma Xiaoyan Deng Guiping Ma |
| author_sort | Xiaokang Wang |
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| description | Neuroblastoma (NB), the most prevalent extracranial solid malignancy in children, poses significant therapeutic challenges, particularly concerning high-risk subtypes characterized by an immunologically “cold” phenotype. These tumors evade immune surveillance through mechanisms such as impaired antigen presentation and immunosuppressive microenvironment formation. Despite the incorporation of immunotherapies (e.g., GD2 monoclonal antibodies) into international clinical guidelines, the 5-year survival rate of patients with NB persistently remains lower than 50%. Small-molecule targeted agents, distinguished by their low molecular weight and superior chemical stability, offer advantages over macromolecular antibody therapies by effectively penetrating cell membranes to engage intracellular targets. Epigenetic regulation, a DNA sequence-independent gene expression modulation system, plays a pivotal role in cell fate determination via dynamic DNA methylation, histone covalent modifications, chromatin spatial reorganization, and non-coding RNA-mediated pathways. Emerging evidence has highlighted a strong correlation between epigenetic dysregulation and NB progression, establishing a molecular rationale for novel therapeutic strategies. Current epigenetic research in NB primarily focuses on histone deacetylase inhibitors and DNA methyltransferase inhibitors. These drugs exhibit unique translational potential because of their accelerated development timelines and cost-effective production, significantly enhancing therapeutic accessibility. This review systematically examines the current landscape of epigenetic modulators in NB treatment and discusses their transformative potential in improving outcomes for high-risk patients with NB. |
| format | Article |
| id | doaj-art-9f06748e9a71485e8f1e03efa9538b4f |
| institution | Matheson Library |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-9f06748e9a71485e8f1e03efa9538b4f2025-07-25T05:25:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16376261637626Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastomaXiaokang Wang0Gengrui Xu1Hongyan Ma2Xiaoyan Deng3Guiping Ma4Department of Pharmacy, Shenzhen Longhua District Central Hospital, Affiliated Longhua Hospital of Shenzhen University, Shenzhen, ChinaDepartment of Pharmacy, Shenzhen Longhua District Central Hospital, Affiliated Longhua Hospital of Shenzhen University, Shenzhen, ChinaDepartment of Pharmacy, Shenzhen Longhua District Central Hospital, Affiliated Longhua Hospital of Shenzhen University, Shenzhen, ChinaCenter of Community Health Service Management, Shenzhen Longhua District Central Hospital, Shenzhen, ChinaBeijing University of Chinese Medicine Affiliated Shenzhen Hospital (Longgang), Shenzhen, ChinaNeuroblastoma (NB), the most prevalent extracranial solid malignancy in children, poses significant therapeutic challenges, particularly concerning high-risk subtypes characterized by an immunologically “cold” phenotype. These tumors evade immune surveillance through mechanisms such as impaired antigen presentation and immunosuppressive microenvironment formation. Despite the incorporation of immunotherapies (e.g., GD2 monoclonal antibodies) into international clinical guidelines, the 5-year survival rate of patients with NB persistently remains lower than 50%. Small-molecule targeted agents, distinguished by their low molecular weight and superior chemical stability, offer advantages over macromolecular antibody therapies by effectively penetrating cell membranes to engage intracellular targets. Epigenetic regulation, a DNA sequence-independent gene expression modulation system, plays a pivotal role in cell fate determination via dynamic DNA methylation, histone covalent modifications, chromatin spatial reorganization, and non-coding RNA-mediated pathways. Emerging evidence has highlighted a strong correlation between epigenetic dysregulation and NB progression, establishing a molecular rationale for novel therapeutic strategies. Current epigenetic research in NB primarily focuses on histone deacetylase inhibitors and DNA methyltransferase inhibitors. These drugs exhibit unique translational potential because of their accelerated development timelines and cost-effective production, significantly enhancing therapeutic accessibility. This review systematically examines the current landscape of epigenetic modulators in NB treatment and discusses their transformative potential in improving outcomes for high-risk patients with NB.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1637626/fullimmunologically coldsmall-molecule targeted agentsepigenetic regulationpediatric neuroblastomatherapeutic strategies |
| spellingShingle | Xiaokang Wang Gengrui Xu Hongyan Ma Xiaoyan Deng Guiping Ma Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastoma Frontiers in Immunology immunologically cold small-molecule targeted agents epigenetic regulation pediatric neuroblastoma therapeutic strategies |
| title | Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastoma |
| title_full | Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastoma |
| title_fullStr | Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastoma |
| title_full_unstemmed | Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastoma |
| title_short | Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastoma |
| title_sort | emerging frontiers in epigenetic targeted therapeutics for pediatric neuroblastoma |
| topic | immunologically cold small-molecule targeted agents epigenetic regulation pediatric neuroblastoma therapeutic strategies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1637626/full |
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