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  3. Exploring fructose metabolism as a potential therapeutic approach for pancreatic cancer

Exploring fructose metabolism as a potential therapeutic approach for pancreatic cancer

  • Cell Death Differ. 2024 Oct 15. doi: 10.1038/s41418-024-01394-3.
Chengqiang Wang 1,  Lu Wang 2,  Qing Zhao 3,  Jiao Ma 1,  Yitao Li 1,  Junliang Kuang 3,  Xintong Yang 1,  Huichang Bi 4,  Aiping Lu 1,  Kenneth C P Cheung 5,  Gerry Melino 6,  Wei Jia 7 8
Affiliations

Affiliations

  • 1 Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
  • 2 Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China.
  • 3 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.
  • 4 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 5 Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. kcpcheung@hkbu.edu.hk.
  • 6 Department of Experimental Medicine, University of Rome "Tor Vergata", 00133, Rome, Italy. melino@uniroma2.it.
  • 7 Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. weijia2@hku.hk.
  • 8 Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China. weijia2@hku.hk.
PMID: 39406919 DOI: 10.1038/s41418-024-01394-3
Abstract

Excessive fructose intake has been associated with the development and progression of pancreatic Cancer. This study aimed to elucidate the relationship between fructose utilization and pancreatic Cancer progression. Our findings revealed that pancreatic Cancer cells have a high capacity to utilize fructose and are capable of converting glucose to fructose via the AKR1B1-mediated polyol pathway, in addition to uptake via the fructose transporter GLUT5. Fructose metabolism exacerbates pancreatic Cancer proliferation by enhancing glycolysis and accelerating the production of key metabolites that regulate angiogenesis. However, pharmacological blockade of fructose metabolism has been shown to slow pancreatic Cancer progression and synergistically enhance anti-tumor capabilities when combined with anti-angiogenic agents. Overall, targeting fructose metabolism may prove to be a promising therapeutic approach in the treatment of pancreatic Cancer.

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