Topic: Power of Epigenetics in Tumor Detection, Treatment, and Prognosis

This special issue will highlight translational research that moves beyond genetic mutations to exploit the dynamic epigenetic landscape of cancer. We seek contributions that leverage multi-omics integration, computational models, and artificial intelligence to develop novel strategies for early detection, risk stratification, and minimal residual disease (MRD) monitoring. In recent years, cell-free DNA (cfDNA) methylation signatures have emerged as highly sensitive biomarkers for multi-cancer early detection (MCED), offering a promising route for non-invasive screening across multiple tumor types. Likewise, advances in fragmentomics and histone modification profiling are revealing new dimensions of tumor biology that can be captured through liquid biopsy, allowing clinicians to monitor treatment response and detect MRD with unprecedented precision. Another frontier of interest is CRISPR-based epigenome editing, which provides a powerful experimental toolkit to validate candidate regulatory regions and epigenetic drivers identified in large-scale datasets. Understanding the temporal dimension of cancer biology through epigenetic clocks also offers insight into tumor evolution, clonal selection, and therapy resistance. Computational approaches are revolutionizing the field, with deep learning frameworks now capable of predicting metastatic potential from primary tumor methylation data, while AI-driven deconvolution techniques enable the dissection of tumor methylation profiles to uncover the immune and stromal components of the tumor microenvironment, which is key to predicting treatment response. This special issue encourages submissions that present integrative AI models combining genetic, epigenetic, and transcriptomic data for robust cancer subtyping and precision oncology. Mapping the epigenetic regulatory networks that drive cancer initiation, progression, and therapy resistance remains a critical challenge, and we welcome studies that use systems biology approaches to address this. Another critical area involves linking somatic mutations in epigenetic modifiers to genome-wide methylation and chromatin dysregulation, enabling a deeper understanding of the causality between genotype and epigenotype. The convergence of epigenomics and radiogenomics is also an exciting area, with the potential to improve cancer detection, therapeutic stratification, and prognostication. Moreover, the integration of radiogenomic and epigenomic features holds promise for predicting immunotherapy response, an urgent need in the era of immune checkpoint blockade. We encourage submissions using single-cell multi-omics (such as scRNA-seq + scATAC-seq) combined with bulk data to dissect intratumoral heterogeneity and identify epigenetically distinct cell states. Emerging technologies such as third-generation sequencing and spatial epigenomics now enable direct, base-level, and spatially resolved measurements of DNA methylation and chromatin accessibility, opening new possibilities for correlating epigenetic signatures with tissue architecture. The field of pharmacoepigenomics is also rapidly advancing, leveraging epigenetic markers to predict response to targeted epigenetic therapies and guide combination treatment strategies, while computational epigenetics for drug repurposing can accelerate the identification of new therapeutic candidates by exploiting known epigenetic signatures and drug-epigenome interactions. Finally, we encourage methodological innovations that aim to develop novel, accurate detection methods, effective treatment strategies, and reliable prognostic tools based on the integration of epigenomic information into clinical workflows. Together, these studies will advance the promise of precision oncology, bringing the power of epigenetics into routine cancer management. The list of suggested topics includes but is not limited to given below.

Suggested Topics for Call for Papers:

● Cell-Free DNA Methylation Signatures for Multi-Cancer Early Detection (MCED);

● The Role of Histone Modifications and Fragmentomics in Liquid Biopsy;
● Epigenetic Liquid Biopsies for Monitoring Treatment Response and Detecting Minimal Residual Disease (MRD);
● CRISPR-based Epigenome Editing for Functional Validation;
● Epigenetic Clocks and Tumor Evolution;
● Deep Learning for Deciphering the Cancer Epigenome: Predicting Metastatic Potential from Primary Tumor Methylation Data;
● AI-Driven Deconvolution of Tumor Methylation Profiles: Unraveling the Tumor Microenvironment;
● Integrative AI Models Combining Genetic, Epigenetic, and Transcriptomic Data for Superior Cancer Subtyping;
● Mapping the Epigenetic Regulatory Networks Driving Cancer Initiation, Treatment, and Progression;
● Integrative Epigenomics: Linking Somatic Mutations in Epigenetic Modifiers to Genome-Wide Epigenetic Dysregulation;
● Integration of Epigenomics and Radiogenomics for Detection, Treatment, and Prognosis of Cancers;
● Integration of Radiogenomics and Epigenomics for Predicting Response to Immunotherapy;
● Single-cell multi-omics (scRNA-seq + scATAC-seq)-combined with Bulk RNA-seq to Dissect Epigenetic Heterogeneity in Tumors;
● The Promise and Challenge of Third-Generation Sequencing for Direct Epigenetic Detection;
● Spatial Epigenomics: Visualizing the Epigenetic Landscape within the Tissue Architecture;
● Pharmacoepigenomics: Using Epigenetic Marks to Predict Response to Epigenetic Therapies;
● NaturalProducts or Synthetic Derivatives for Epigenetic Regulation and Therapeutics in Cancers;
● Computational Epigenetics for Drug Repurposing;
● Develop Novel Methods for Accurate Detection, Effective Treatment, and Reliable Prognosis of Cancers.

Suggested Article Types to Solicit:

● Original Research:The core of the issue;

● Comprehensive Reviews:On the topics above, summarizing the state of the art;

● Methodological Articles:Describing new bioinformatics pipelines or AI models for epigenetic data analysis;

● Brief Communications:Reporting on novel, high-impact preliminary findings;

● Perspectives/Commentaries:From leaders in the field on future directions and challenges.