Epigenetics in Human Cancer: Emerging Biomarkers and Therapeutic Targets

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 4558

Special Issue Editor


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Guest Editor
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea
Interests: cancer biology; translational research; breast cancer; epigenetics; drug resistance; cancer stem cells; epithelial-mesenchymal transition; tumor metastasis; tumor microenvironment
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Special Issue Information

Dear Colleagues,

Beyond genetic alterations, epigenetic changes are increasingly recognized as critical drivers in the initiation, progression, and therapeutic resistance of human cancers. Aberrant DNA methylation and histone modifications frequently lead to the activation of oncogenes or the silencing of tumor suppressor genes.

A growing body of evidence highlights the role of epigenetic regulators in orchestrating key cancer hallmarks, including tumorigenesis, uncontrolled proliferation, survival, metastasis, immune evasion, metabolic reprogramming, and resistance to therapy. These insights have positioned epigenetic mechanisms not only as vital elements of cancer biology but also as promising biomarkers and therapeutic targets. In particular, epigenetic-based therapies—either alone or in combination with chemotherapy, targeted therapy, or immunotherapy—are showing potential to overcome resistance and improve patient outcomes.

This Special Issue aims to provide a comprehensive overview of the epigenetic mechanisms in human cancer. We welcome original research articles and reviews that explore recent advances in cancer epigenetics, novel therapeutic targets, biomarker development, and clinical applications related to epigenetic dysregulation across various cancer types.

Topics of interest include, but are not limited to:

  • DNA methylation and demethylation in cancer;
  • Histone modifications and chromatin remodeling regulating cancer-associated genes;
  • The role of non-coding RNAs (miRNAs, lncRNAs, circRNAs) in cancer;
  • Epigenetic therapies to overcome anti-cancer drug resistance;
  • Epigenetic reprogramming of the tumor microenvironment;
  • Clinical applications and biomarkers based on epigenetic alterations.

We look forward to your valuable contributions to this Special Issue, hoping for them to advance the understanding and clinical application of epigenetics in oncology.

Prof. Dr. Jeong-yeon Lee
Guest Editor

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Keywords

  • cancer
  • epigenetics
  • DNA methylation
  • histone modification
  • chromatin remodeling
  • non-coding RNAs
  • therapeutic resistance

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Published Papers (2 papers)

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Review

24 pages, 1329 KB  
Review
The Great Potential of DNA Methylation in Triple-Negative Breast Cancer: From Biological Basics to Clinical Application
by Wanying Xie, Ying Wen, Siqi Gong, Qian Long and Qiongyan Zou
Biomedicines 2026, 14(1), 241; https://doi.org/10.3390/biomedicines14010241 - 21 Jan 2026
Viewed by 1144
Abstract
Triple-negative breast cancer (TNBC), which is characterized by a lack of the estrogen receptor, the progesterone receptor, and HER2 expression, is the most aggressive breast cancer subtype and has a poor prognosis and high recurrence rates because of frequent chemotherapy resistance. As a [...] Read more.
Triple-negative breast cancer (TNBC), which is characterized by a lack of the estrogen receptor, the progesterone receptor, and HER2 expression, is the most aggressive breast cancer subtype and has a poor prognosis and high recurrence rates because of frequent chemotherapy resistance. As a crucial epigenetic regulator, DNA methylation modulates gene expression through aberrant methylation patterns, contributing to tumor progression and therapeutic resistance. Early diagnosis and treatment of TNBC are vital for its prognosis. The development of DNA methylation testing technology and the application of liquid biopsy provide technological support for early diagnosis and treatment. Additionally, preclinical and early-phase clinical studies suggest that epigenetic therapies targeting DNA methylation may hold promise for TNBC treatment, pending larger clinical trials. Furthermore, research on DNA methylation-based prognostic models enables personalized precision treatment for patients, helping to reduce unnecessary therapies and improve overall survival. The emerging role of DNA methylation patterns in predicting the therapeutic response and overcoming drug resistance is highlighted. In this narrative review, we integrate current research findings and clinical perspectives. We propose that DNA methylation presents promising research prospects for the diagnosis, treatment and prognosis prediction of TNBC. Future efforts should focus on translating methylation-driven insights into clinically actionable strategies, ultimately advancing precision oncology for this challenging disease. Full article
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36 pages, 3215 KB  
Review
NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities
by Jae Eun Park, Minh Tuan Nguyen, Jaehee Kim, Chang Hoon Lee, Jin-Wu Nam, Heekyoung Chung, Mi Kyung Park and Jeong-Yeon Lee
Biomedicines 2025, 13(11), 2749; https://doi.org/10.3390/biomedicines13112749 - 11 Nov 2025
Cited by 1 | Viewed by 3068
Abstract
Histone H3 lysine 36 (H3K36) methylation, a pivotal epigenetic mark that ensures transcriptional fidelity and genomic integrity, plays an essential role in development and tumorigenesis. The nuclear receptor-binding SET domain (NSD) family of histone methyltransferases, comprising NSD1, NSD2, and NSD3, primarily catalyzes mono- [...] Read more.
Histone H3 lysine 36 (H3K36) methylation, a pivotal epigenetic mark that ensures transcriptional fidelity and genomic integrity, plays an essential role in development and tumorigenesis. The nuclear receptor-binding SET domain (NSD) family of histone methyltransferases, comprising NSD1, NSD2, and NSD3, primarily catalyzes mono- and di-methylation of H3K36 (H3K36me1/2) and engages with chromatin-associated and transcriptional regulatory complexes in a context-dependent manner. Increasing evidence demonstrates that NSD family members have emerged as critical drivers in human cancers. Recurrent gene amplifications, point mutations, and oncogenic fusions of NSD family genes are frequently observed in both solid and hematologic cancers. Their dysregulation contributes to tumorigenesis, cancer cell proliferation and survival, and metastatic progression through both H3K36 methylation-dependent and -independent mechanisms. Pharmacological inhibition of NSD catalytic activity, as well as alternative approaches such as targeted protein degradation or disruption of cofactor interactions, are emerging as promising therapeutic strategies for cancer treatment. This review summarizes the structural features, molecular functions, and cancer-associated alterations and mechanisms of the NSD family and highlights recent advances in targeting these enzymes as potential epigenetic vulnerabilities in cancer. Full article
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