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Cell Biology
Unlocking the Mechanisms of Cutaneous Adverse Drug Reactions: Activation of the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway by EGFR Inhibitors Triggers Keratinocyte Differentiation and Polarization of Epidermal Immune Responses
EGFR inhibitors used in oncology therapy modify the keratinocyte differentiation processes, impairing proper skin barrier formation and leading to cutaneous adverse drug reactions. To uncover the molecular signatures associated with cutaneous adverse drug reactions, we applied phosphoproteomic and transcriptomic assays on reconstructed human epidermis tissues exposed to a therapeutically relevant concentration of afatinib, a second-generation EGFR inhibitor. After drug exposure, we observed activation of the phosphatidylinositol 3-kinase/protein kinase B pathway associated with an increased expression of gene families involved in keratinocyte differentiation, senescence, oxidative stress, and alterations in the epidermal immune-related markers.
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