Cell-Free Nucleic Acids in Gastrointestinal Cancers: From Molecular Insights to Clinical Applications

Gastrointestinal (GI) cancers remain a major global health burden, accounting for substantial cancer-related morbidity and mortality worldwide. Cell-free and extracellular nucleic acids (eNAs), including cell-free DNA (cfDNA), extracellular RNA (eRNA), and nucleic acid structures associated with neutrophil extracellular traps (NETs), are increasingly recognized as dynamic, functional components of the tumor ecosystem rather than mere byproducts of cellular turnover. In GI cancers, accumulating evidence suggests that these extracellular nucleic acids contribute to tumor progression, metastasis, immune modulation, and therapy resistance.Beyond their established role in diagnostics and liquid biopsy, extracellular nucleic acids represent an emerging and underexplored class of therapeutic targets. Cancer-derived eDNA and eRNA can influence cellular behavior through multiple mechanisms, including horizontal transfer of oncogenic signals, modulation of gene expression, and interaction with cell surface and intracellular nucleic acid-sensing systems.Recent studies highlight the role of NETs in promoting tumor growth, metastatic niche formation, and immune evasion in GI malignancies. Additionally, emerging nucleic acid-sensing receptor systems, including recently described TezR receptors, may mediate the sensing and functional responses of tumor and immune cells, representing a potentially paradigm-shifting mechanism of intercellular communication.This Research Topic aims to gather innovative and interdisciplinary research and perspectives on the functional role of extracellular nucleic acids in GI cancers, with a particular emphasis on mechanistic insights and translational opportunities for therapeutic targeting. We welcome original research, reviews, and conceptual articles addressing:Topics of interest include, but are not limited to:• biological characteristics and release mechanisms of cell-free nucleic acids in gastrointestinal cancers• biological functions of cancer-derived extracellular DNA and RNA in gastrointestinal cancers• NETs and their contribution to GI cancer progression and metastasis• Role of TezR receptors in gastrointestinal malignancies • strategies to therapeutically target extracellular nucleic acids or their associated pathways• preclinical and translational studies exploring extracellular nucleic acid–targeted interventions This Research Topic welcomes Original Research, Reviews, Systematic Reviews, and other article types that contribute to advancing knowledge in this rapidly evolving and clinically relevant field.Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: George Tetz, Allan Tsung, Victor Tetz Source: https://www.frontiersin.org/research-topics/79556/cell-free-nucleic-acids-in-gastrointestinal-cancers-from-molecular-insights-to-clinical-applications