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

Michiaki Nakajo1,2, Tomonobu Uchino3,4,5, Kazuhiro Asada6

  • 1Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.

Cancer Chemotherapy and Pharmacology
|July 2, 2026
PubMed
Abstract

Insights

Osimertinib treatment alters stratum corneum lipids, reducing their chain length and disrupting skin barrier structure, leading to hand-foot syndrome. This research compares lipid changes in healthy skin versus Osimertinib-induced HFS.

Area of Science:

  • Dermatology
  • Oncology
  • Biochemistry

Background:

  • Osimertinib (OSM), a third-generation EGFR inhibitor, is used for non-small cell lung cancer.
  • OSM can cause skin disorders like hand-foot syndrome (HFS), impairing skin barrier function.
  • Stratum corneum (SC) lipids are crucial for maintaining skin barrier integrity.

Purpose of the Study:

  • To compare the SC lipid composition and structure in healthy individuals versus patients with OSM-induced HFS.
  • To investigate the molecular basis of skin barrier dysfunction caused by OSM.

Main Methods:

  • Analyzed SC lipid composition (ceramides and free fatty acids) using UPLC-MS/MS.
  • Assessed SC lipid structure using synchrotron X-ray diffraction.
  • Compared samples from 7 patients with OSM-induced HFS (OSC) and healthy controls (HSC).

Main Results:

  • Healthy SC exhibited two lamellar phases and specific hydrocarbon chain packing.
  • OSC showed a near-complete loss of these ordered lipid structures.
  • SC lipids in OSC had reduced carbon chain lengths compared to HSC, affecting CER and FFA composition.

Conclusions:

  • OSM treatment alters SC lipid composition and decreases lipid chain length.
  • These changes disrupt the SC lipid structure, leading to impaired skin barrier function and HFS.
  • Specific CER levels involved in lamellar structure formation remained unchanged.
Keywords:
Osimertinibceramidehand-foot syndromelamellar structurelateral structurestratum corneum

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