Epigenetics and Metabolism: A Close Liaison in Tumor Cells – Volume II

This Research Topic is the second volume of: Epigenetics and Metabolism: A Closed Liaison in Tumor CellsEpigenetics and metabolism are increasingly recognized as tightly interconnected regulators of tumor cell fate. Recent evidence demonstrates that many epigenetic enzymes rely on key cellular metabolites - such as acetyl-CoA, S-adenosylmethionine, NAD+, and α-ketoglutarate - as substrates or cofactors, enabling dynamic changes in chromatin organization and gene expression without altering the underlying DNA sequence. Cancer cells, through mutations and environmental pressures, undergo metabolic rewiring that not only fulfills bioenergetic and biosynthetic needs but also fundamentally transforms the epigenetic landscape. This bi-directional crosstalk influences transcriptional plasticity, enables tumor heterogeneity, and shapes the tumor’s response to therapy. Despite rapid advances, fundamental questions persist regarding the precise molecular mechanisms, scope, and therapeutic exploitation of these intertwined pathways, particularly as new ‘omics’ technologies reveal greater complexity in tumor cell adaptation, lineage switching, and resistance.This Research Topic aims to unite pioneering studies that dissect how metabolic reprogramming in tumor cells orchestrates epigenetic modifications, and reciprocally, how epigenetic states regulate cellular metabolism during cancer progression. By gathering multi-disciplinary work - from molecular mechanisms and integrative multi-omics to translational studies and targeted therapies - we seek to clarify the drivers of tumor initiation, evolution, plasticity, metastasis, and drug resistance rooted in metabolic–epigenetic interplay. We further invite investigations that interrogate the consequences of existing or novel metabolic and epigenetic therapies, biomarkers for clinical stratification, and innovative model systems that help untangle the causal chains linking metabolism, epigenetics, and malignancy.The scope of this Research Topic encompasses basic, pre-clinical, and translational investigations addressing the intersection of metabolism and epigenetics in tumor biology. This includes in vitro, in vivo, or computational approaches, with a focus on cancer-specific innovations and therapeutic developments. To gather further insights into this evolving field, we welcome articles addressing, but not limited to, the following themes:• Metabolite-dependent regulation of chromatin and DNA modifications in tumor cells• One-carbon metabolism, methylation, and their role in oncogenesis• Oncometabolites (e.g., 2-hydroxyglutarate, succinate, fumarate) and epigenomic dysregulation• Non-canonical histone modifications/acylations and chromatin accessibility• 3D genome organization in the context of metabolic reprogramming• Tumor cell plasticity, stemness, dormancy, and lineage flexibility• Microenvironment-derived metabolic cues and epigenetic adaptation• Epigenetic and metabolic mechanisms underlying therapy response and resistance• Single-cell, spatial, and multi-omics approaches to tumor state heterogeneity• Therapeutic strategies co-targeting metabolism and epigenetic regulators Topic editors: Serena Castelli, Rohan Kodgule Source: https://www.frontiersin.org/research-topics/80507/epigenetics-and-metabolism-a-close-liaison-in-tumor-cells---volume-ii