{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:53:20Z","timestamp":1787961200418,"version":"build-2784847793"},"reference-count":94,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The tyrosine kinase activity of epidermal growth factor receptors (EGFRs) plays critical roles in cell proliferation, regeneration, tumorigenesis, and anticancer resistance. Non-small-cell lung cancer patients who responded to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and obtained survival benefits had somatic EGFR mutations. EGFR-TKI-related adverse events (AEs) are usually tolerable and manageable, although serious AEs, including lung injury (specifically, interstitial lung disease (ILD), causing 58% of EGFR-TKI treatment-related deaths), occur infrequently. The etiopathogenesis of EGFR-TKI-induced ILD remains unknown. Risk factors, such as tobacco exposure, pre-existing lung fibrosis, chronic obstructive pulmonary disease, and poor performance status, indicate that lung inflammatory circumstances may worsen with EGFR-TKI treatment because of impaired epithelial healing of lung injuries. There is limited evidence from preclinical and clinical studies of the mechanisms underlying EGFR-TKI-induced ILD in the available literature. Herein, we evaluated the relationship between EGFR-TKIs and AEs, especially ILD. Recent reports on mechanisms inducing lung injury or resistance in cytokine-rich circumstances were reviewed. We discussed the relevance of cytotoxic agents or immunotherapeutic agents in combination with EGFR-TKIs as a potential mechanism of EGFR-TKI-related lung injury and reviewed recent developments in diagnostics and therapeutics that facilitate recovery from lung injury or overcoming resistance to anti-EGFR treatment.<\/jats:p>","DOI":"10.3390\/ijms22020792","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T11:39:14Z","timestamp":1610624354000},"page":"792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury"],"prefix":"10.3390","volume":"22","author":[{"given":"Tohru","family":"Ohmori","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6182-6047","authenticated-orcid":false,"given":"Toshimitsu","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan"},{"name":"Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sojiro","family":"Kusumoto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunari","family":"Kishino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryou","family":"Manabe","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2376-1606","authenticated-orcid":false,"given":"Hironori","family":"Sagara","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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