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Epigenetics in Cancer and Drug Therapeutics

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 10 May 2026 | Viewed by 3040

Special Issue Editors


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Guest Editor
Department of Surgery, Center for Precision Medicine, University of Wisconsin Madison, Wisconsin, WI 53705, USA
Interests: cancer; pancreatic cancer; cancer epigenetics; molecular target; cancer therapeutics

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Guest Editor
Department of Surgery, Yale School of Medicine, New Haven, CT 06520, USA
Interests: appendiceal cancer; epigenetics; translational research; cancer biomarkers; gastrointestinal cancer; precision oncology; epigenetic-specific biomarker
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Special Issue Information

Dear Colleagues,

Epigenetics is pivotal in cancer biology, shaping the chromatin landscape and regulating gene expression dynamically and reversibly. Alterations in chromatin regulators and spatial genome organization are increasingly recognized as central drivers of cancer aggressiveness, metastasis, and therapeutic resistance. Techniques like Hi-C have illuminated how genome architecture contributes to these phenotypes, uncovering actionable vulnerabilities. Meanwhile, epigenetic therapies targeting DNMTs, HDACs, and chromatin-binding proteins have shown promise in reprogramming tumor epigenomes and enhancing immune modulation. This call for papers invites researchers to contribute innovative studies that dissect these mechanisms and explore their therapeutic implications. Together, let us advance our understanding of epigenetic plasticity in cancer and translate these findings into impactful interventions. Submit your work to help shape the future of epigenetic cancer research and therapy.

We invite submissions for a Special Issue exploring the intricate relationship between epigenetics and cancer, emphasizing translating epigenetic findings into innovative therapeutic strategies. This issue seeks to present cutting-edge research on the molecular underpinnings of cancer, focusing on chromatin regulation, spatial genome organization, and their impact on disease progression and therapeutic resistance.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  1. The role of chromatin remodeling complexes and histone modifiers in tumorigenesis and therapy resistance.
  2. Spatial genome architecture: insights from Hi-C and other 3D genome mapping techniques in understanding cancer aggressiveness and progression.
  3. The development and validation of DNA methylation, histone modification, or chromatin accessibility markers for diagnosis and treatment response.
  4. The development of small-molecule inhibitors or biologics targeting epigenetic regulators (e.g., DNMT, HDAC, proteins).
  5. Insights from single-cell and spatial epigenomics in dissecting intra-tumoral diversity and microenvironmental influences.
  6. Uncovering epigenetic mechanisms that drive metastasis, recurrence, and poor prognosis and associated therapeutic drug-based approaches.
  7. The synergistic use of epigenetic drugs with immune checkpoint inhibitors or other immunotherapeutics.

We look forward to receiving your contributions.

Dr. Bethsebie Sailo
Dr. Anup R. Sharma
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer epigenetics
  • chromatin remodeling complexes
  • histone modifiers
  • DNA methylation
  • molecular target
  • cancer therapy

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Published Papers (2 papers)

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Review

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26 pages, 1487 KB  
Review
Epigenetic Regulation of Higher-Order Chromatin Structure (HOCS) and Its Implication in Human Diseases
by Luisa Ladel, Bethsebie Sailo, Paromita Das, Ethan Samuel Lin, Wan Ying Tan, Ankit Chhoda, Haoyu Tang, Olivia Ang-Olson, Linda He, Nithyla John, Jeremy D. Kratz, Anup Sharma and Nita Ahuja
Cancers 2026, 18(3), 483; https://doi.org/10.3390/cancers18030483 (registering DOI) - 31 Jan 2026
Abstract
This review explores how DNA folds into 3D higher-order chromatin structures that regulate gene activity. It highlights how epigenetic mechanisms and architectural proteins work together to shape the dynamic chromatin folding while allowing structural flexibility based on cellular needs. Disruption of these folding [...] Read more.
This review explores how DNA folds into 3D higher-order chromatin structures that regulate gene activity. It highlights how epigenetic mechanisms and architectural proteins work together to shape the dynamic chromatin folding while allowing structural flexibility based on cellular needs. Disruption of these folding patterns leads to aberrant gene regulation, contributing to cancer, aging-related disorders, and certain congenital conditions. We emphasize specific genomic regions and epigenetic modulators that act as regulatory hubs for 3D organization, which could serve as promising biomarkers or therapeutic targets for cancer. Overall, it underscores the importance of a deeper understanding of DNA’s large-scale 3D architecture for advancing precision medicine and developing novel diagnostic approaches for cancer and other human diseases. Full article
(This article belongs to the Special Issue Epigenetics in Cancer and Drug Therapeutics)

Other

Jump to: Review

29 pages, 3313 KB  
Systematic Review
Epigenetic Reprogramming by Decitabine in Triple-Negative Breast Cancer: Mechanisms, Immune Modulation, and Therapeutic Synergy
by Fathima Raahima Riyas Mohamed, Safiah Aldubaisi, Arshiya Akbar, Mohammad Imran Khan and Ahmed Yaqinuddin
Cancers 2025, 17(18), 2953; https://doi.org/10.3390/cancers17182953 - 9 Sep 2025
Cited by 2 | Viewed by 2516
Abstract
Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 expression, with limited targeted therapies and poor outcomes. Epigenetic dysregulation, particularly aberrant DNA methylation, is a key driver. Decitabine, a DNA methyltransferase inhibitor (DNMTi), shows promise by reactivating [...] Read more.
Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 expression, with limited targeted therapies and poor outcomes. Epigenetic dysregulation, particularly aberrant DNA methylation, is a key driver. Decitabine, a DNA methyltransferase inhibitor (DNMTi), shows promise by reactivating silenced tumor suppressor genes and modulating immune responses. This systematic review evaluates preclinical and clinical evidence on decitabine’s efficacy, mechanisms, and translational potential in TNBC. Methods: A PRISMA-2020 compliant search of PubMed, EBSCO, Web of Science, and Semantic Scholar was conducted up to April 2025. Included studies assessed decitabine alone or in combination in TNBC preclinical or clinical settings. Risk of bias was assessed using QUIPS and RoB 2.0 tools. Results: Twenty-five studies were included. In vitro, decitabine-induced growth inhibition, apoptosis, and re-expression of silenced genes (such as BRCA1 and CDH1). In vivo, it reduced tumor burden and enhanced anti-tumor immunity through MHC-I, PD-L1, and STING pathway upregulation. Synergy was noted with anti-PD-1, HDAC inhibitors, and chemotherapy. Resistance mechanisms included persistent DNMT activity, low DCK, and miRNA-driven escape (miR-155–TSPAN5). Conclusions: Decitabine demonstrates strong preclinical and early clinical potential in TNBC via epigenetic reprogramming and immune activation. Future strategies should focus on biomarker-based selection and resistance mitigation. Full article
(This article belongs to the Special Issue Epigenetics in Cancer and Drug Therapeutics)
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