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Volume 18, Issue 1 (March-2026 2026)
Iranian Journal of Blood and Cancer 2026, 18(1): 124-137 |
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Kumar Singh V, Singh Matreja P, Kumar A, Awasthi S. GLUT5 and Cancer Progression: A Systematic Review of High Fructose Diets in Tumor Growth. Iranian Journal of Blood and Cancer 2026; 18 (1) :124-137
URL: http://ijbc.ir/article-1-1809-en.html
URL: http://ijbc.ir/article-1-1809-en.html
1- Department of General Medicine, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. , drvinodkumarsingh85@gmail.com
2- Department of Pharmacology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India.
3- Department of Pathology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India.
2- Department of Pharmacology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India.
3- Department of Pathology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India.
Abstract: (651 Views)
Background: The global rise in fructose consumption has raised concerns about its role in cancer biology. Unlike glucose, fructose is selectively transported by GLUT5, which is aberrantly expressed in several malignancies. Enhanced GLUT5 activity may fuel metabolic reprogramming and promote tumor progression, but evidence across experimental and clinical studies remains heterogeneous.
Objective: This systematic review aimed to consolidate evidence on the role of GLUT5 in mediating the effects of high fructose intake on tumor growth and to evaluate its potential as a therapeutic target.
Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for studies published between January 2000 and August 2024. Eligible studies included in vitro, in vivo, and clinical investigations assessing GLUT5 expression under high fructose conditions in relation to tumor outcomes. Data extraction and quality assessment were performed independently by two reviewers using the Modified Coleman Methodology Score (MCMS).
Results: Thirty-two studies were included (18 in vitro, 10 in vivo, 4 clinical). High fructose exposure consistently upregulated GLUT5 expression, with a 2–3-fold increase in mRNA and protein levels. Elevated GLUT5 correlated with greater tumor volume (+40–60%), higher proliferation rates (+30–50%), and increased invasiveness compared with controls (p < 0.05). Subgroup analyses showed the strongest effects in colorectal and breast cancers, while pancreatic and hepatocellular carcinoma models demonstrated enhanced invasiveness and accelerated onset. Mechanistically, GLUT5-driven fructose uptake activated glycolytic and lipogenic pathways, as well as PI3K/Akt/mTOR signaling and EMT-related changes, supporting tumor aggressiveness.
Conclusions: Evidence indicates that a high fructose diet contributes to tumor progression through GLUT5-mediated metabolic reprogramming. While preclinical findings are compelling, clinical validation remains limited. Standardization of fructose dosing protocols, integration of human dietary studies, and evaluation of GLUT5-targeted interventions are urgently needed. GLUT5 holds promise as a biomarker and therapeutic target in fructose-associated oncogenesis.
Objective: This systematic review aimed to consolidate evidence on the role of GLUT5 in mediating the effects of high fructose intake on tumor growth and to evaluate its potential as a therapeutic target.
Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for studies published between January 2000 and August 2024. Eligible studies included in vitro, in vivo, and clinical investigations assessing GLUT5 expression under high fructose conditions in relation to tumor outcomes. Data extraction and quality assessment were performed independently by two reviewers using the Modified Coleman Methodology Score (MCMS).
Results: Thirty-two studies were included (18 in vitro, 10 in vivo, 4 clinical). High fructose exposure consistently upregulated GLUT5 expression, with a 2–3-fold increase in mRNA and protein levels. Elevated GLUT5 correlated with greater tumor volume (+40–60%), higher proliferation rates (+30–50%), and increased invasiveness compared with controls (p < 0.05). Subgroup analyses showed the strongest effects in colorectal and breast cancers, while pancreatic and hepatocellular carcinoma models demonstrated enhanced invasiveness and accelerated onset. Mechanistically, GLUT5-driven fructose uptake activated glycolytic and lipogenic pathways, as well as PI3K/Akt/mTOR signaling and EMT-related changes, supporting tumor aggressiveness.
Conclusions: Evidence indicates that a high fructose diet contributes to tumor progression through GLUT5-mediated metabolic reprogramming. While preclinical findings are compelling, clinical validation remains limited. Standardization of fructose dosing protocols, integration of human dietary studies, and evaluation of GLUT5-targeted interventions are urgently needed. GLUT5 holds promise as a biomarker and therapeutic target in fructose-associated oncogenesis.
Keywords: GLUT5, Fructose, High Fructose Diet, Tumor Growth, Cancer Metabolism, Fructose Transporter, Systematic Review
: Review Article |
Subject:
Adults Hematology & Oncology
Received: 2025/12/6 | Accepted: 2026/03/14 | Published: 2026/03/31
Received: 2025/12/6 | Accepted: 2026/03/14 | Published: 2026/03/31
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