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

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

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)5540-5545
Number of pages6
JournalBiological Trace Element Research
Issue number12
StatePublished - 12 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.


  • Hand-foot skin reaction
  • Intracellular zinc homeostasis
  • SLC30 and SLC39 zinc transporters
  • Tyrosine kinase inhibitor
  • Zinc deficiency


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