ArticleSignal transduction and targeted therapy2022
Gefitinib and fostamatinib target EGFR and SYK to attenuate silicosis: a multi-omics study with drug exploration.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 79 citations in OpenAlex.
- Targeting SLK protects against cerebral ischemia-reperfusion injury by regulating USP8-mediated HIF-1α stabilization and RhoA/ROCK activation.Cellular & molecular biology letters · 2026Article
- MFN2 Overexpression Attenuates Coal Dust-Induced Pulmonary Fibrosis by Modulating MAMs Integrity and Cell Apoptosis.Toxics · 2026Article
- The dynamic landscape of alternative splicing during silicosis progression.Respiratory research · 2026Article
- Systematic Proteomic Characterization of EV-A71-Infected Mice Identifies Dynamic Molecular Changes and Therapeutic Targets.MedComm · 2026Article
- The network pharmacology prediction and experiment validation of Astragalus membranaceus for alleviating silicosis fibrosis via decreasing MMP9 and EGFR expression.Scientific reports · 2026Article
- Integrated analysis of gut microbiome and fecal metabolome reveals potential non-invasive biomarkers for early-stage silicosis.Microbiology spectrum · 2026Article
- Identification of PANoptosis-related genes in lung cancer and investigation of their role mechanisms in the immune microenvironment.Discover oncology · 2026Article
- Zearalenone exposure may increase the risk of non-alcoholic fatty liver disease by activating CYP1B1-SCD1.Current research in toxicology · 2026Article
- Stem cell-based therapies for silicosis: mechanisms, sources, clinical translation, and emerging strategies.Frontiers in immunology · 2026Review
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- Review
- Ferroptosis and iron metabolism drive fibroblast activation in silicosis: insights from a novel 3D lung matrix model.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis.Journal of advanced research · 2025Article
- The pathogenicity and multi-organ proteomic profiles of Mpox virus infection in SIVmac239-infected rhesus macaques.Nature communications · 2025Article
- Fibroblast EGFR signaling mediates ricin toxin-induced acute lung injury via EGR1/CXCL1 axis.Archives of toxicology · 2025Article
- Developing a novel aging assessment model to uncover heterogeneity in organ aging and screening of aging-related drugs.Genome medicine · 2025Article
- Homoharringtonine exerts anti-silicosis potential by inhibiting the CCR1 and PI3K/AKT signaling pathways in lung fibroblasts.Journal of biomedical research · 2025Article
- Article
- TTK Inhibition Alleviates Postinjury Neointimal Formation and Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role of environmental pollutants-induced ferroptosis in pulmonary diseases.Frontiers in medicine · 2025Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics, and currently used drugs cannot reverse the disease progress. Worse still, there are still challenges to be addressed to fully decipher the intricated pathogenesis. Thus, specifying the essential mechanisms and targets in silicosis progression then exploring anti-silicosis pharmacuticals are desperately needed. In this work, multi-omics atlas was constructed to depict the pivotal abnormalities of silicosis and develop targeted agents. By utilizing an unbiased and time-resolved analysis of the transcriptome, proteome and phosphoproteome of a silicosis mouse model, we have verified the significant differences in transcript, protein, kinase activity and signaling pathway level during silicosis progression, in which the importance of essential biological processes such as macrophage activation, chemotaxis, immune cell recruitment and chronic inflammation were emphasized. Notably, the phosphorylation of EGFR (p-EGFR) and SYK (p-SYK) were identified as potential therapeutic targets in the progression of silicosis. To inhibit and validate these targets, we tested fostamatinib (targeting SYK) and Gefitinib (targeting EGFR), and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis. Overall, our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of silicosis.
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