Research ArticleSKIN DISORDERS

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

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Science Translational Medicine  11 Dec 2019:
Vol. 11, Issue 522, eaax2693
DOI: 10.1126/scitranslmed.aax2693

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The skinny on a cancer drug side effect

Therapeutics targeting the epidermal growth factor receptor (EGFR) are used for many cancer types, but they have notable side effects, including a potentially severe and disfiguring skin rash. Klufa et al. discovered that the inhibition of EGFR interferes with the ability of skin stem cells to reestablish a secure barrier after it is broken in the process of hair eruption. This loss of skin barrier integrity permits microorganisms to invade the skin and trigger inflammation similar to that which occurs in atopic dermatitis. The authors also identified a pathway that could be targeted to protect the skin without restoring EGFR activity directly.


Epidermal growth factor receptor (EGFR)–targeted anticancer therapy induces stigmatizing skin toxicities affecting patients’ quality of life and therapy adherence. The lack of 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 and prevent the invasion of commensal microbiota and inflammatory skin disease. EGFR-deficient epidermis is permissive for microbiota outgrowth and displays an atopic-like TH2-dominated signature. The opening of the follicular ostia during hair eruption allows invasion of commensal microbiota into the hair follicle, initiating an additional TH1 and TH17 response culminating in chronic folliculitis. Restoration of epidermal ERK signaling via prophylactic FGF7 treatment or transgenic SOS expression rescues the barrier defect in the absence of EGFR, highlighting a therapeutic anchor point. These data reveal that commensal skin microbiota provoke atopic-like inflammatory skin diseases by invading into the follicular opening of erupting hair.

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