Skin Barrier Dysfunction, Antimicrobial Peptide Alterations, and Microbiome Changes in Solid Cancer Patients Treated with Epidermal Growth Factor Receptor Inhibitors

INTRODUCTION: Epidermal growth factor receptor inhibitors (EGFRIs) are targeted therapies for solid cancers. Their use is associated with cutaneous adverse events (cAEs). This study aimed to investigate cAEs and changes in skin biophysics reflecting the skin barrier function, alterations in antimicrobial peptides (AMPs), and the skin microbiome in patients undergoing treatment with EGFRIs. METHODS: A 2-year prospective cohort study was conducted involving patients receiving EGFRIs for solid cancers. cAEs and skin biophysical properties, including transepidermal water loss (TEWL), skin pH, elasticity, sebum, and pigmentation, were measured at baseline and follow-up visits up to 48 weeks. AMPs were assessed using a tape-stripping technique from the cheeks at months 0, 1, and 6, with protein assays and ELISA to determine the levels of human beta-defensin (hBD)-3 and ribonuclease (RNase)-7. Skin microbiome analysis was performed through 16S rRNA sequencing of cheek swabs collected at months 0, 1, and 6. RESULTS: Eighty-four patients were enrolled. The cumulative incidence of cAEs was 94.05%. Skin biophysical properties showed significantly increased TEWL and pH, decreased pigmentation, and no significant changes in elasticity and sebum. AMP analysis from 15 patients revealed significant reduction of RNase-7 levels after 6 months into EGFRIs, while hBD-3 level change was insignificant. A microbiome study from 18 patients showed statistically increased Corynebacterium kroppenstedtii at months 1 and 6, while Cutibacterium acnes, Corynebacterium aurimucosum, Staphylococcus epidermidis, and Staphylococcus aureus were not significantly different among groups. CONCLUSION: Treatment with EGFRIs compromises skin barrier function and AMP production, leading to skin microbiota changes.