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High glucose: an emerging association between diabetes mellitus and cancer progression

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Abstract

The association of cancer and diabetes mellitus (DM) has been studied for decades. Hyperglycemia and the imbalance of hormones are factors that contribute to the molecular link between DM and carcinogenesis and cancer progression. Hyperglycemia alone or in combination with hyperinsulinemia are key factors that promote cancer aggressiveness. Many preclinical studies suggest that high glucose induces abnormal energy metabolism and aggressive cancer via several mechanisms. As evidenced by clinical studies, hyperglycemia is associated with poor clinical outcomes in patients who have comorbid DM. The prognoses of cancer patients with DM are improved when their plasma glucose levels are controlled. This suggests that high glucose level maybe be involved in the molecular mechanism that causes the link between DM and cancer and may also be useful for prognosis of cancer progression. This review comprehensively summarizes the evidence from recent pre-clinical and clinical studies of the impact of hyperglycemia on cancer advancement as well as the underlying molecular mechanism for this impact. Awareness among clinicians of the association between hyperglycemia or DM and cancer progression may improve cancer treatment outcome in patients who have DM.

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Acknowledgements

Charupong Saengboonmee (PMAYP-10612) and Suangson Supabphol (PMAYP-10615) are awardees of Prince Mahidol Award Youth Program from Prince Mahidol Award Foundation under the Royal Patronage of HM the King of Thailand. Charupong Saengboonmee is also supported by Professor Peter Sicinski for his visiting program at Dana-Farber Cancer Institute and Harvard Medical School. We acknowledge help from Dr. Treerat Mahankasuwan, Khu Muang Hospital, Buriram, Thailand, for generating the illustrations and would like to thank Dr. Justin T. Reese for editing the manuscript via the Publication Clinic at KKU, Thailand.

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Authors and Affiliations

  1. The Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Suangson Supabphol

  2. Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Wunchana Seubwai

  3. Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand

    Wunchana Seubwai, Sopit Wongkham & Charupong Saengboonmee

  4. Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Wunchana Seubwai, Sopit Wongkham & Charupong Saengboonmee

  5. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Sopit Wongkham & Charupong Saengboonmee

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  1. Suangson Supabphol
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  2. Wunchana Seubwai
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Conceptualization: Suangson Supabphol, Wunchana Seubwai, Sopit Wongkham, and Charupong Saengboonmee. Review literature: Suangson Supabphol and Charupong Saengboonmee. Writing first draft of manuscript: Suangson Supabphol and Charupong Saengboonmee. Supervision, review, and editing of the manuscript: Wunchana Seubwai and Sopit Wongkham. All authors contribute to critically review and approve the final manuscript.

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Correspondence to Charupong Saengboonmee.

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Supabphol, S., Seubwai, W., Wongkham, S. et al. High glucose: an emerging association between diabetes mellitus and cancer progression. J Mol Med 99, 1175–1193 (2021). https://doi.org/10.1007/s00109-021-02096-w

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