Editorial: Epigenetics and metabolism: a closed liaison in tumor cells

The Research Topic Epigenetics and Metabolism: A Closed Liaison in Tumor Cells was conceived with the aim of gathering multidisciplinary contributions focused on this intricate and fascinating crosstalk. The articles collected in this issue highlight how metabolic intermediates, chromatin modifications, non-coding RNAs, and transcriptional regulators converge to modulate cancer cell fate and tumor evolution. Together, these works provide a contemporary overview of the epi-metabolic networks underlying malignancy and identify emerging therapeutic vulnerabilities.Among the contributions included in this Special Issue, the review by Bansal and colleagues discusses the epigenetic consequences of reducing sugars and glycation products in cancer, emphasizing how metabolic alterations associated with glycation may profoundly influence chromatin organization and transcriptional regulation. Their work reinforces the concept that metabolic byproducts are not passive consequences of tumor metabolism but active signaling molecules capable of driving oncogenic programs https://doi.org/10.3389/freae.2025.1752493. Finally, the review by Akdaş and colleagues examines the role of the NAD(H)-dependent corepressor CTBP1 as a molecular sensor integrating metabolic cues with transcriptional and oncogenic programs https://doi.org/10.3389/fimmu.2026.1797122. This work exemplifies how metabolic cofactors can directly regulate epigenetic and transcriptional machinery, reinforcing the concept that metabolism and epigenetics cannot be studied as isolated processes in cancer biology.Collectively, the studies presented in this Research Topic support the idea that the metabolic state of tumor cells is deeply interconnected with epigenetic plasticity. Metabolites such as acetyl-CoA, Sadenosylmethionine, α-ketoglutarate, succinate, fumarate, and NAD+ are now recognized as crucial regulators of chromatin-modifying enzymes and transcriptional activity. Conversely, epigenetic alterations reshape glucose, lipid, and amino acid metabolism, thereby sustaining the malignant phenotype and contributing to intratumoral heterogeneity and therapy resistance (Dai et al., 2024).Despite significant progress, many questions remain unresolved. Future studies will need to better define the temporal dynamics of epi-metabolic interactions, their tumor-specific context dependency, and their contribution to metastatic dissemination and drug resistance. In parallel, advances in singlecell and spatial multi-omics technologies will likely provide unprecedented opportunities to dissect the heterogeneity of these processes within the tumor microenvironment. We believe that deciphering this "closed liaison" will not only improve our understanding of tumor biology but also pave the way toward innovative therapeutic strategies capable of simultaneously targeting metabolic and epigenetic vulnerabilities in cancer cells.Author contributions SC: Writing-original draft, Writing-review and editing. NM: Writing-review and editing. RK: Writing-review and editing.