Research Progress and Challenges in Targeting GLUT1 in Tumors

The solute carrier family 2 member 1 (SLC2A1), which encodes glucose transporter 1 (GLUT1), has long been recognized as a key driver of aerobic glycolysis in cancer. However, accumulating evidence has substantially expanded this view, revealing that GLUT1 functions not only as a critical mediator of metabolic reprogramming but also as an important regulator linking tumor metabolism to immune evasion. Notably, GLUT1 expression, regulation, and functional dependence are highly context-dependent across tumor types, disease states, and cellular compartments. Recent studies further link GLUT1-dependent glycolytic flux to immune regulation through glucose competition, lactate accumulation, and metabolite-dependent epigenetic programs within the tumor microenvironment. Reflecting this evolving understanding, therapeutic strategies targeting GLUT1 have progressed from simple metabolic inhibition to approaches that exploit tumor-specific metabolic dependencies and extend to regulated cell death, combination therapy, precision delivery, and selective modulation of malignant and non-malignant cellular compartments. These advances support a shift from expression-centered targeting toward strategies guided by functional GLUT1 dependence and cellular context, while recognizing the metabolic and physiological constraints that shape the therapeutic window. In this review, we systematically summarize recent advances in GLUT1 expression heterogeneity, multilayered regulatory networks, metabolic-immune crosstalk, diagnostic and prognostic relevance, and therapeutic targeting, and discuss how these insights may refine biomarker development, patient selection, and the clinical translation of GLUT1-directed precision metabolic therapy.