Research Progress and Challenges in Targeting GLUT1 in Tumors
- 1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Abstract
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.
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BibTeX
@article{chen2026research,
title = {{Research Progress and Challenges in Targeting GLUT1 in Tumors}},
author = {Taohua Chen and Bi Peng and Xinya Yuan and Yizhou Liu and Jianing Zhang and Yizhen Su and Guangyuan Hu and Zhen Tao and Guoxian Long},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209225},
url = {https://www.mdpi.com/1422-0067/27/20/9225},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Research Progress and Challenges in Targeting GLUT1 in Tumors
AU - Taohua Chen
AU - Bi Peng
AU - Xinya Yuan
AU - Yizhou Liu
AU - Jianing Zhang
AU - Yizhen Su
AU - Guangyuan Hu
AU - Zhen Tao
AU - Guoxian Long
PY - 2026
DA - 2026/10/17
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209225
UR - https://www.mdpi.com/1422-0067/27/20/9225
AB - 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.
SN - 1422-0067
ER -