Trial reportScience translational medicine2013
Genetic ablation of epidermal EGFR reveals the dynamic origin of adverse effects of anti-EGFR therapy.
Trial report in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 104 citations in OpenAlex.
- Neurokinin-1 antagonist orvepitant for EGFRI-induced pruritus in patients with cancer: a randomised, placebo-controlled phase II trial.BMJ open · 2020Trial
- Dermatologic Toxicities Associated With Novel Pan-RAS/RAF Inhibitors.Journal of cutaneous pathology · 2026Article
- ABL209 (NEOK002): Designing an EGFR × MUC1 Bispecific TOP1i ADC with Promising Antitumor Activity and Enhanced Therapeutic Window.Molecular cancer therapeutics · 2026Article
- Airway epithelial cell-specific deletion of EGFR modulates mucoinflammatory features of cystic fibrosis-like lung disease in mice.Frontiers in immunology · 2025Article
- JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia.EMBO molecular medicine · 2024Article
- Cancer Therapy-induced Dermatotoxicity as a Window to Understanding Skin Immunity.Hematology/oncology clinics of North America · 2024Review
- Traditional Chinese Medicine Formulae QY305 Reducing Cutaneous Adverse Reaction and Diarrhea by its Nanostructure.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Diseases categorized as autoinflammatory keratinization diseases (AiKDs), and their pathologies and treatments.Nagoya journal of medical science · 2024Review
- Menahydroquinone-4 may play a key role in regulating CCL5 expression induced by epidermal growth factor receptor inhibitors.Scientific reports · 2023Article
- EGFR marks a subpopulation of dermal mesenchymal cells highly expressing IGF1 which enhances hair follicle regeneration.Journal of cellular and molecular medicine · 2023Article
- The Riddle of Cetuximab-Related Skin Toxicity:Cancers · 2022Article
- Remodeling of dermal adipose tissue alleviates cutaneous toxicity induced by anti-EGFR therapy.eLife · 2022Article
- The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function.Frontiers in cell and developmental biology · 2022Review
- Therapeutic targets and signaling mechanisms of dasatinib activity against radiation skin ulcer.Frontiers in public health · 2022Article
- Composition and Bioactivity of a Modified Huang-Lian-Jie-Du Decoction.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Article
- Article
- [Establishment of animal models of epidermal growth factor receptor inhibitor-related rashes].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Comparison of gefitinib-induced skin adverse reactions (SAR) in C57BL/6 and FVB/N mice.Toxicology research · 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
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer patients treated with anti-EGFR (epidermal growth factor receptor) drugs often develop a dose-limiting pruritic rash of unknown etiology. The aims of our study were to define causal associations from a clinical study of cutaneous and systemic changes in patients treated with gefitinib and use these to develop and characterize a mouse model that recapitulates the human skin rash syndrome caused by anti-EGFR therapy. We examined the patients' plasma before and after treatment with gefitinib and documented changes in chemokines and leukocyte counts associated with the extent of rash or the presence of pruritus. We established a parallel mouse model by ablating EGFR in the epidermis. These mice developed skin lesions similar to the human rash. Before lesion development, we detected increased mRNA expression of chemokines in the skin associated with early infiltration of macrophages and mast cells and later infiltration of eosinophils, T cells, and neutrophils. As the skin phenotype evolved, changes in blood counts and circulating chemokines reproduced those seen in the gefitinib-treated patients. Crossing the mutant mice with mice deficient for tumor necrosis factor-α (TNF-α) receptors, MyD88, NOS2, CCR2, T cells, or B cells failed to reverse the skin phenotype. However, local depletion of macrophages provided partial resolution, suggesting that this model can identify targets that may be effective in preventing the troublesome and dose-limiting skin response to anti-EGFR drugs. These results highlight the importance of EGFR signaling in maintaining skin immune homeostasis and identify a macrophage contribution to a serious adverse consequence of cancer chemotherapy.
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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.