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A Potential Association of Zinc Deficiency and Tyrosine Kinase Inhibitor-Induced Hand-Foot Skin Reaction

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Abstract

Hand-foot skin reaction (HFSR) is a common skin-related adverse event induced by multikinase inhibitors targeting both platelet-derived growth factor receptor and vascular endothelial growth factor receptor, possibly due to inadequate repair following frictional trauma. Zinc is a trace element and essential nutrient in humans that plays critical roles in the development and differentiation of skin cells. Zinc transporters (Zrt- and Irt-like proteins and Zn transporters) and metallothioneins are involved in zinc efflux, uptake, and homeostasis and have been reported to be involved in skin differentiation. The underlying mechanism of HFSR remains unclear, and the association between HFSR and zinc has not been previously studied. However, some case reports and case series provide potential evidence to suggest that zinc deficiency may be involved in HFSR development and zinc supplementation may relieve HFSR symptoms. However, no large-scale clinical studies have been conducted to examine this role. Therefore, this review summarizes the evidence supporting a possible link between HFSR development and zinc and proposes potential mechanisms underlying this association based on current evidence.

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Acknowledgements

This work was supported by grants from Linkou Chang Gung Memorial Hospital in Taiwan. Please refer to funding section.

Funding

This research was funded by Linkou Chang Gung Memorial Hospital (CMRPG3K2171 to CEW) and National Science and Technology Council (NSTC 109-2314-B-182-080-MY3 to CEW).

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Authors and Affiliations

  1. Department of General Surgery and Liver Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan

    Chun-Nan Yeh, Sheng-Hsuan Lin & Yi-Ru Pan

  2. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Chun-Nan Yeh, Wen-Kuan Huang, Chun-Wei Lu, Chiao-Ping Chen, Sheng-Hsuan Lin, Yi-Ru Pan & Chiao-En Wu

  3. Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan, 333, Taiwan

    Wen-Kuan Huang, Chiao-Ping Chen & Chiao-En Wu

  4. Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan

    Chun-Wei Lu

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  1. Chun-Nan Yeh
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Contributions

Y.W. was involved in the conception, organization, writing, and editing of the manuscript. W.L.C.L.P. collected literature and data. Y.H.L.W. was involved in the research, writing, and editing of the manuscript. Y.L.W. revised the manuscript critically for important intellectual content. W. supervised the final editing of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Chiao-En Wu.

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Yeh, CN., Huang, WK., Lu, CW. et al. A Potential Association of Zinc Deficiency and Tyrosine Kinase Inhibitor-Induced Hand-Foot Skin Reaction. Biol Trace Elem Res 201, 5540–5545 (2023). https://doi.org/10.1007/s12011-023-03618-y

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