The inflammation–epigenetics axis in gastrointestinal cancers: Mechanisms and therapeutic frontiers

Chronic inflammation is a well-established driver of gastrointestinal (GI) cancers, yet the molecular crosstalk underlying this relation is not fully defined. Emerging evidence reveals that inflammatory mediators such as IL-6, TNF-α, and NF-κB initiate and sustain tumorigenesis by reprogramming the epigenetic landscape—inducing DNA methylation, histone modifications, and dysregulation of non-coding RNAs. These changes alter gene expression profiles, silence tumor suppressor genes, compromise DNA repair mechanisms, and facilitate immune evasion, epithelial-to-mesenchymal transition (EMT), and unchecked proliferation. This Research Topic seeks to illuminate the dynamic interplay between inflammation and epigenetic regulation in GI malignancies—including esophageal, gastric, pancreatic, liver, and colorectal cancers. We welcome original research, reviews, and perspectives that investigate mechanistic links, identify novel epigenetic biomarkers, or propose targeted therapeutic strategies. A better understanding of this axis may unlock new opportunities for early detection, risk stratification, and epigenetic or immunologic interventions across the GI cancer spectrum.

A major challenge in gastrointestinal (GI) oncology is the treatment of therapy-resistant tumors and the lack of reliable, non-invasive biomarkers to identify high-risk patients early in disease progression. Recent discoveries have shown that chronic inflammation not only drives oncogenic mutations but also induces profound epigenetic reprogramming—such as promoter hypermethylation, histone modifications, and dysregulation of non-coding RNAs—that shape tumor phenotype, immune evasion, and drug resistance. These epigenetic shifts are often reversible, dynamic, and detectable before overt malignancy, offering a unique therapeutic and diagnostic opportunity.

The goal of this Research Topic is to harness recent mechanistic insights into the inflammation–epigenetics axis to advance two key areas: (1) the development of novel epigenetic-based therapies to overcome resistance in GI cancers, and (2) the identification of early, non-invasive epigenetic biomarkers—such as circulating methylated DNA or miRNAs—for risk stratification and surveillance. We encourage submissions that translate basic findings into clinical innovations, highlight promising therapeutic targets, or explore cutting-edge technologies like liquid biopsy and spatial epigenomics to improve outcomes in GI oncology.

We are especially interested in studies that:

• Elucidate signaling pathways (e.g., NF-κB, JAK/STAT3) linking inflammation to epigenetic remodeling
• Identify novel epigenetic biomarkers (e.g., circulating miRNAs, methylated DNA) for early, non-invasive cancer detection or risk stratification
• Examine how epigenetic drift contributes to therapeutic resistance and tumor plasticity
• Propose or evaluate epigenetic-targeting agents (e.g., DNMTis, HDACis) for GI cancers
• Apply cutting-edge technologies such as spatial transcriptomics, single-cell epigenomics, or liquid biopsy platforms
• Explore inflammation–epigenetics crosstalk in specific GI malignancies, including esophageal, gastric, pancreatic, and colorectal cancers

We invite original research articles, systematic or narrative reviews, mini-reviews, perspectives, and hypothesis-driven opinion pieces that align with these themes.