Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.

Glucose metabolism reprogramming as a defining hallmark of cancer has become a pivotal frontier in oncology research. Recent technological advances in single-cell sequencing, spatial omics, and metabolic imaging have transformed the field from static bulk analyses to dynamic investigations of spatiotemporal heterogeneity at a single-cell resolution. This review systematically summarizes the current knowledge on tumor glucose metabolism dynamics, discussing spatial heterogeneity and temporal evolution patterns, metabolic subpopulation interactions revealed by single-cell metabolomics, the glucose metabolism-epigenetics-immunology regulatory axis, and therapeutic strategies targeting metabolic vulnerabilities. Recent technological advances in single-cell sequencing and spatial omics have transformed our understanding of tumor glucose metabolism by providing high-resolution insights into metabolic heterogeneity and regulatory mechanisms, contrasting with classical bulk analyses. Spatiotemporal heterogeneity critically influences therapeutic outcomes by enabling tumor cells to adapt metabolically under selective pressures (e.g., hypoxia, nutrient deprivation), fostering treatment resistance and relapse. Deciphering these dynamics is essential for developing spatiotemporally targeted strategies that address intratumoral diversity and microenvironmental fluctuations. By integrating cutting-edge advances, this review deepens our understanding of tumor metabolic complexity and provides a conceptual framework for developing spatiotemporally precise interventions.