Hair eruption initiates and commensal skin microbiota aggravate adverse events of anti-EGFR therapy

• DOI: 10.1126/scitranslmed.aax2693
• Publication Date: 2019-12-12T00:15:41Z
• Authors: Jörg Klufa; Thomas Bauer; Buck Hanson; Craig Herbold; Philipp Starkl; Beate Lichtenberger; Dagmar Srutkova; Daniel Schulz; Igor Vujic; Thomas Mohr; Klemens Rappersbe...; Bernd Bodenmiller; Hana Kozakova; Sylvia Knapp; Alexander Loy; Maria Sibilia
• Keywords: Epidermis (zoology); Folliculitis

Epidermal growth factor receptor (EGFR)-targeted anticancer therapy induces stigmatizing skin toxicities affecting patients' quality of life and adherence. The lack mechanistic details underlying these adverse events hampers their management. We found that EGFR/ERK signaling is required in LRIG1-positive stem cells during de novo hair eruption to secure barrier integrity prevent the invasion commensal microbiota inflammatory disease. EGFR-deficient epidermis permissive for outgrowth displays an atopic-like TH2-dominated signature. opening follicular ostia allows into follicle, initiating additional TH1 TH17 response culminating chronic folliculitis. Restoration epidermal ERK via prophylactic FGF7 treatment or transgenic SOS expression rescues defect absence EGFR, highlighting a therapeutic anchor point. These data reveal provoke diseases by invading erupting hair.