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Purpose <p>Osimertinib (OSM), a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, causes skin disorders, such as hand-foot syndrome (HFS), which impairs skin barrier function. Stratum corneum (SC) lipids play an important role in skin barrier function. This study aimed to compare the SC lipid composition and structure of healthy participants with those of patients with OSM-induced HFS.</p> Methods <p>Overall, 47 patients with non-small cell lung cancer were enrolled in this study. All patients received 80&#xa0;mg/day OSM orally and completed the 56-day prospective observation period. SC samples were obtained from seven patients with OSM-induced HFS (OSC). SC lipid composition (ceramide [CER] and free fatty acids [FFAs]) and structure were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and synchrotron X-ray diffraction, respectively.</p> Results <p>In healthy SC (HSC), the lipids formed two lamellar phases. Hexagonal and orthorhombic hydrocarbon chain packing was observed in the lateral lipid organization. However, in the OSC, these structures almost disappeared. UPLC-MS/MS analysis revealed that the composition of CER and FFA differed between OSC and HSC and that the carbon chain length of SC lipid components in OSCs was lower compared with that in HSCs. However, no significant differences were observed in the CER levels of the esterified ω-hydroxy fatty acid class, which is involved in the formation of long-period lamellar structures, between the two groups.</p> Conclusion <p>OSM induces changes in SC lipid structure due to changes in SC lipid composition and a decrease in carbon chain length in OSCs, resulting in impaired barrier function.</p>

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Composition and structure of stratum corneum intercellular lipids in patients with osimertinib-induced hand-foot syndrome

  • 期刊论文

  • 发表日期：

    2026年7月2日

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  • Michiaki Nakajo,
  • Tomonobu Uchino,
  • Kazuhiro Asada,
  • Ichiro Hatta,
  • Ryuji Yumoto,
  • Mayuko Okada,
  • Yuna Iwano,
  • Yui Nabekura,
  • Yasunori Miyazaki,
  • Kanami Ikeda,
  • Tasuku Yokoyama,
  • Yoshiyuki Kagawa,
  • Daiki Tsuji

摘要

Purpose

Osimertinib (OSM), a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, causes skin disorders, such as hand-foot syndrome (HFS), which impairs skin barrier function. Stratum corneum (SC) lipids play an important role in skin barrier function. This study aimed to compare the SC lipid composition and structure of healthy participants with those of patients with OSM-induced HFS.

Methods

Overall, 47 patients with non-small cell lung cancer were enrolled in this study. All patients received 80 mg/day OSM orally and completed the 56-day prospective observation period. SC samples were obtained from seven patients with OSM-induced HFS (OSC). SC lipid composition (ceramide [CER] and free fatty acids [FFAs]) and structure were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and synchrotron X-ray diffraction, respectively.

Results

In healthy SC (HSC), the lipids formed two lamellar phases. Hexagonal and orthorhombic hydrocarbon chain packing was observed in the lateral lipid organization. However, in the OSC, these structures almost disappeared. UPLC-MS/MS analysis revealed that the composition of CER and FFA differed between OSC and HSC and that the carbon chain length of SC lipid components in OSCs was lower compared with that in HSCs. However, no significant differences were observed in the CER levels of the esterified ω-hydroxy fatty acid class, which is involved in the formation of long-period lamellar structures, between the two groups.

Conclusion

OSM induces changes in SC lipid structure due to changes in SC lipid composition and a decrease in carbon chain length in OSCs, resulting in impaired barrier function.