Host Systemic Metabolism and Cancer Metabolic Vulnerabilities: Mechanisms and Therapeutic Opportunities

Cancer metabolism has traditionally been studied as a tumor cell–intrinsic phenomenon, with a focus on pathways such as glycolysis, glutaminolysis, and lipid metabolism. However, mounting evidence highlights that tumor metabolic behavior is profoundly influenced by host systemic metabolism in the host, including endocrine signals, nutrient availability, organ–organ communication, and whole-body metabolic states such as obesity, diabetes, and cachexia. These systemic factors dynamically shape the tumor microenvironment and contribute to metabolic heterogeneity and plasticity within tumors.Recent advancements in metabolomics, flux analysis, and in vivo modeling have enabled deeper exploration of the mechanisms by which systemic metabolic conditions regulate tumor growth, immune responses, and therapeutic sensitivity. Of particular significance is the growing recognition that metabolic interactions between tumors and host tissues—such as liver, muscle, adipose tissue, and gut microbiota—are emerging as critical determinants of cancer progression and treatment outcomes. Despite these advances, an integrated understanding of how systemic metabolism creates exploitable cancer-specific metabolic vulnerabilities remains incomplete. Bridging this gap is essential for developing effective metabolism-based therapeutic strategies.The goal of this Research Topic is to provide a comprehensive and integrative framework linking host systemic metabolism with tumor metabolic vulnerabilities. We aim to highlight mechanistic insights, technological advances, and translational approaches that uncover how systemic metabolic states influence cancer development, progression, and therapy response. By bringing together contributions from basic scientists, clinicians, and computational researchers, this collection seeks to identify novel metabolic dependencies and actionable targets shaped by systemic physiology. Ultimately, the Research Topic will support the development of innovative therapeutic strategies that exploit the interplay between host metabolism and tumor biology.We welcome original research, reviews, and perspectives addressing, but not limited to, the following themes:● Interactions between systemic metabolism (e.g., obesity, diabetes, cachexia) and tumor metabolic reprogramming● Organ–tumor metabolic crosstalk (e.g., liver, muscle, adipose tissue, microbiome)● Nutrient availability and metabolic competition in the tumor microenvironment● Metabolic regulation of anti-tumor immunity and immunotherapy response● Identification of systemic-driven metabolic vulnerabilities in cancer● Metabolism-based therapeutic strategies and combination treatments● Role of diet, fasting, or metabolic interventions in cancer progression and therapy● Advanced metabolomics, fluxomics, and in vivo metabolic tracing approaches● Integrated computational and experimental models of systemic–tumor metabolic interactions 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: Marisabel Mecca, Huseyin Aydin, GRAZIELLA MARINO Source: https://www.frontiersin.org/research-topics/79885/host-systemic-metabolism-and-cancer-metabolic-vulnerabilities-mechanisms-and-therapeutic-opportunities