Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose homeostasis

Lin, Minglin; Jin, Junfei

doi:10.1038/nrclinonc.2017.56

Cited by 3 publications

(1 citation statement)

References 16 publications

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“…Many pre-clinical studies have investigated use of [ 18 F]FDG PET imaging for TKI treatment monitoring, and some studies showed early changes in [ 18 F]FDG levels while others did not 4 . Depending on the TKI used, accumulating evidence show either increased or decreased glucose levels in patients during TKI therapy, although dasatinib, erlotinib, sunitinib, and sorafenib were shown to lower glucose levels and improve glycemic control 5 . PET tracer uptake is complex and depends on tumor type, targeted kinase, and tracer uptake by tumors.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on ¹⁸F‐FDG PET Uptake

Damaraju

Aminpour

Kuzma

et al. 2021

Clinical Translational Sci

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Positron emission tomography (PET) using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG), a marker of energy metabolism and cell proliferation, is routinely used in the clinic to assess patient response to chemotherapy and to monitor tumor growth. Treatment with some tyrosine kinase inhibitors (TKIs) causes changes in blood glucose levels in both non-diabetic and diabetic patients. We evaluated the interaction of several classes of TKIs with human glucose transporter-1 (hGLUT-1) in FaDu and GIST-1 cells by measuring [ 3 H]2-deoxy-D-glucose ([ 3 H]2-DG) and [ 3 H]FDG uptake. Uptake of both was inhibited to varying extents by the TKIs, and representative TKIs from each class showed competitive inhibition of [ 3 H]2-DG uptake. In GIST-1 cells, [ 3 H]FDG uptake inhibition by temsirolimus and nilotinib was irreversible, whereas inhibition by imatinib, gefitinib, and pazopanib was reversible. Molecular modeling studies showed that TKIs form multiple hydrogen bonds with polar residues of the sugar binding site (i.e., Q161, Q282, Q283, N288, N317, and W388), and van der Waals interactions with the H-pocket site. Our results showed interaction of TKIs with amino acid residues at the glucose binding site to inhibit glucose uptake by hGLUT-1. We showed that inhibition of hGLUT-1 by TKIs could alter glucose levels in patients treated with TKIs, leading to hypoglycemia and fatigue, although further studies are required to evaluate roles of other SLC2 and SLC5 members. In addition, TKIs could affect tumor [ 18 F]FDG uptake, increasingly used as a marker of tumor response. hGLUT-1 inhibition by TKIs may have implications for routine [ 18 F]FDG-PET monitoring of tumor response in patients.

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Section: Introductionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on ¹⁸F‐FDG PET Uptake

Damaraju

Aminpour

Kuzma

et al. 2021

Clinical Translational Sci

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Endokrine Nebenwirkungen von Tumortherapien

Braegelmann,

Führer,

Tan

2024

Innere Medizin

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Ageing – Oxidative stress, PTMs and disease

Ebert

Tran

Schurgers

et al. 2022

Molecular Aspects of Medicine

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Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose homeostasis

Cited by 3 publications

References 16 publications

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on ¹⁸F‐FDG PET Uptake

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on ¹⁸F‐FDG PET Uptake

Endokrine Nebenwirkungen von Tumortherapien

Ageing – Oxidative stress, PTMs and disease

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Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose homeostasis

Cited by 3 publications

References 16 publications

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on 18F‐FDG PET Uptake

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on 18F‐FDG PET Uptake

Endokrine Nebenwirkungen von Tumortherapien

Ageing – Oxidative stress, PTMs and disease

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Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on ¹⁸F‐FDG PET Uptake

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on ¹⁸F‐FDG PET Uptake