ArticleOncotarget2016
Epidermal growth factor receptor inhibitors trigger a type I interferon response in human skin.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
- Novel Immunotherapy Agents in Early-Phase Trials for Head and Neck Cancer.JAMA network open · 2026Article
- Role of E5 from HPV16 in the Evasion of the Immune Response.International journal of molecular sciences · 2026Review
- Pharmacovigilance analysis of cutaneous adverse drug reactions for cetuximab, panitumumab, and necitumumab based on EudraVigilance and WHO VigiAccess.Frontiers in pharmacology · 2026Article
- RNAi-based ALOX15B silencing augments keratinocyte inflammation in vitro via EGFR/STAT1/JAK1 signalling.Cell death & disease · 2025Article
- Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.The Journal of investigative dermatology · 2024Article
- A Critical Role for IFN-β Signaling for IFN-κ Induction in Keratinocytes.Frontiers in lupus · 2024Article
- Role of ErbB and IL-1 signaling pathways in the dermonecrotic lesion induced by Loxosceles sphingomyelinases D.Archives of toxicology · 2023Article
- Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy.Molecular therapy oncolytics · 2022Article
- Exploration of the Potential Mechanism of Qi Yin San Liang San Decoction in the Treatment of EGFRI-Related Adverse Skin Reactions Using Network Pharmacology andFrontiers in oncology · 2022Article
- Quercetin attenuates viral infections by interacting with target proteins and linked genes in chemicobiological models.In silico pharmacology · 2022Article
- Article
- Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep.BMC biology · 2021Article
- Intracellular lipid droplet accumulation occurs early following viral infection and is required for an efficient interferon response.Nature communications · 2021Article
- Studying Immunotherapy Resistance in a Melanoma Autologous Humanized Mouse Xenograft.Molecular cancer research : MCR · 2021Article
- Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response.Journal of translational medicine · 2021Article
- A hybrid systems biology and systems pharmacology investigation of Zingerone's effects on reconstructed human epidermal tissues.The Egyptian journal of medical human genetics · 2021Article
- A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer.British journal of cancer · 2021Article
- Role of Immune Checkpoint Inhibitor Therapy in AdvancedFrontiers in oncology · 2021Review
- The influence of interferon on healthy and diseased skin.Cytokine · 2020Review
- Polymorphisms of NF-κB pathway genes influence adverse drug reactions of gefitinib in NSCLC patients.The pharmacogenomics journal · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Epidermal Growth Factor Receptor (EGFR) is centrally involved in the regulation of key processes of the epithelia, including cell proliferation, survival, differentiation, and also tumorigenesis. Humanized antibodies and small-molecule inhibitors targeting EGFR were developed to disrupt these functions in cancer cells and are currently used in the treatment of diverse metastatic epithelial cancers. By contrast, these drugs possess significant skin-specific toxic effects, comprising the establishment of a persistent inflammatory milieu. So far, the molecular mechanisms underlying these epiphenomena have been investigated rather poorly. Here we showed that keratinocytes respond to anti-EGFR drugs with the development of a type I interferon molecular signature. Upregulation of the transcription factor IRF1 is early implicated in the enhanced expression of interferon-kappa, leading to persistent activation of STAT1 and further amplification of downstream interferon-induced genes, including anti-viral effectors and chemokines. When anti-EGFR drugs are associated to TNF-α, whose expression is enhanced by the drugs themselves, all these molecular events undergo a dramatic enhancement by synergy mechanisms. Finally, high levels of interferon-kappa can be observed in epidermal keratinocytes and also in leukocytes infiltrating the upper dermis of cetuximab-driven skin lesions. Our data suggest that dysregulated activation of type I interferon innate immunity is implicated in the molecular processes triggered by anti-EGFR drugs and leading to persistent skin inflammation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.