Targeting fructose metabolism for cancer therapy

Qing Zhao; Wen-Lian Chen; Gerry Melino; Wei Jia

doi:10.1016/j.canlet.2025.217914

Targeting fructose metabolism for cancer therapy

Cancer Lett. 2025 Jul 11:631:217914. doi: 10.1016/j.canlet.2025.217914. Online ahead of print.

Authors

Qing Zhao¹, Wen-Lian Chen², Gerry Melino³, Wei Jia⁴

Affiliations

¹ Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
² Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
³ Department of Experimental Medicine, University of Rome "Tor Vergata", 00133, Rome, Italy. Electronic address: melino@uniroma2.it.
⁴ Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China. Electronic address: weijia2@hku.hk.

PMID: 40653188
DOI: 10.1016/j.canlet.2025.217914

Abstract

Cancer cells frequently rewire their metabolism to support rapid proliferation and invasion. Our analysis of the most lethal cancers in 2022 reveals a prominent association with dysregulated fructose metabolism. Fructose serves as a crucial alternative energy substrate under nutrient-deprived conditions, promoting the Warburg effect and thereby facilitating tumor growth and metastasis. Moreover, aberrant fructose utilization activates oncogenic mTORC1 signaling, suppresses anti-tumor immune responses, and facilitates tumor progression. Targeting key enzymes and transporters in fructose metabolism presents a promising therapeutic avenue to disrupt tumor bioenergetics and signaling pathways, potentially improving treatment efficacy and patient outcomes.

Keywords: Combined treatment strategy; Extended treatment window; Fructose metabolism; Tumor malignancy; Warburg effect.

Publication types

Review