Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury

• Published in: International journal of molecular sciences 2021-01, Vol.22 (2), p.792
• Main Authors: Ohmori, Tohru, Yamaoka, Toshimitsu, Ando, Koichi, Kusumoto, Sojiro, Kishino, Yasunari, Manabe, Ryou, Sagara, Hironori
• Format: Article
• Language: English
• Subjects: Acne; Acrylamides - adverse effects; Acrylamides - therapeutic use; Adverse events; Afatinib - adverse effects; Afatinib - therapeutic use; Aniline Compounds - adverse effects; Aniline Compounds - therapeutic use; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Cell proliferation; Chemotherapy; Chronic obstructive pulmonary disease; Cytokines; Cytotoxic agents; Cytotoxicity; Drugs; EGFR-TKIs; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Fibrosis; Gefitinib - adverse effects; Gefitinib - therapeutic use; Growth factor receptors; Growth factors; Health services; Humans; Inflammation; Injury prevention; Lung cancer; Lung diseases; Lung Diseases, Interstitial - chemically induced; Lung Diseases, Interstitial - diagnosis; lung injury; Lung Injury - chemically induced; Lung Injury - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Medical prognosis; Mutation; Obstructive lung disease; Patients; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Quality of life; Review; Risk analysis; Risk factors; Skin; Skin diseases; TNF; Tobacco; Tumorigenesis; Tyrosine; Wound healing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22020792

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.