Metabolic disease and the cancer stem cell niche: stromal reprogramming, epigenetic convergence, and therapeutic resistance

Cancer stem cells (CSCs) depend on a permissive niche to survive, and that niche is shaped by more than tumour biology alone. Chronic metabolic conditions, particularly diabetes and hypertension, reconfigure stromal behaviour, rewire epigenetic programmes, and activate signalling networks that sustain stem-like identity and protect malignant populations from treatment. Despite the clinical reality that cancer and metabolic disease frequently co-occur, this biological relationship remains underexplored as a unified research question.In haematological malignancies, the bone marrow stromal microenvironment is a well-established driver of leukemic stem cell maintenance and chemoresistance. Notch, Wnt, and Hedgehog signalling, central to normal haematopoietic stem cell fate, are co-opted within this niche to sustain quiescent, drug-tolerant populations. Chronic hyperglycaemia and hypertension-associated vascular inflammation further alter stromal and epigenetic landscapes in ways that reinforce these programmes, while insulin and IGF signalling link systemic metabolic dysregulation directly to survival pathways in malignant stem-like cells. In solid tumours, parallel mechanisms operate through DNA methylation, miRNA dysregulation, and extracellular vesicle-mediated stromal-CSC crosstalk, contributing to resistance across chemotherapy, targeted agents, and immune checkpoint inhibitors, and connecting metabolic comorbidity to CSC biology in settings from pancreatic to lung cancer.We welcome contributions that address, but are not limited to:Cancer stem cell identity, plasticity, and niche dependence in haematological and solid malignanciesHaematopoietic stem cell niche regulation under conditions of metabolic disease, including diabetes, hypertension, and metabolic syndromeNotch, Wnt, Hedgehog, and insulin/IGF signalling in CSC maintenance and niche-mediated therapy resistanceStromal cell reprogramming by chronic metabolic disease and its consequences for leukemic and solid tumour stem cell survivalExtracellular vesicles as mediators of stromal-CSC crosstalk and drivers of therapeutic resistanceEpigenetic mechanisms — DNA methylation, histone remodelling, miRNAs, and non-coding RNAs — at the interface of metabolic disease and cancer stem cell biologyBiomarkers of niche reprogramming and metabolic-oncological crosstalk predictive of treatment responseResistance to chemotherapy, targeted therapy, and immune checkpoint inhibition in the context of chronic metabolic comorbidityClinical and translational perspectives on CSC-targeting strategies in patients with concurrent metabolic diseaseWe encourage Original Research, Reviews, Mini Reviews, Methods, and Perspective articles from researchers working across basic science, translational medicine, and clinical practice.This Research Topic is associated with the Global Conference on Cancer, Chronic Disease & Equity (GC3E 2026), convened by the Association Hypertension Diabetes Cancer in Canada (AHDCC) and hosted at the University of Saskatchewan, Canada, 27–30 November 2026. Conference participants are warmly encouraged to submit their work, though the collection is open to all researchers working in relevant areas. Topic editors: Armel Hervé Nwabo Kamdje, Giorgio Malpeli, Paul F. Seke Etet Source: https://www.frontiersin.org/research-topics/81337/metabolic-disease-and-the-cancer-stem-cell-niche-stromal-reprogramming-epigenetic-convergence-and-therapeutic-resistance