POTENTIAL OTOTOXIC EFFECTS OF DIFFERENT GENERATIONS OF EGFR TYROSINE KINASE INHIBITORS: A LITERATURE REVIEW

L. BALYMBETOVA, Yerbolat Maratovich Iztleuov, Elnara K. Ismagulova, Sarkyt Kozhantayeva, Gulmira Iztleuova

2025

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DOI 10.52532/2521-6414-2025-3-77-423
Data confidence 70 medium
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Abstract

Relevance: Lung cancer is one of the most frequent malignant tumors, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases. Mutations in the epidermal growth factor receptor (EGFR) gene contribute significantly to NSCLC development. EGFR is key for tumor occurrence and progression. The discovery of tyrosine kinase inhibitors (TKI) targeting EGFR has marked significant progress, offering a more rational and effective therapeutic approach. However, TKIs are not free of side effects. Evidence indicates a potential link between TKI therapy and ototoxicity. Given the chronic nature of the treatment of patients with advanced stages of the disease, even minor toxicity can significantly affect the quality of life. It is essential to inform patients about the potential risk of hearing impairment and to regularly monitor for early signs of ototoxicity, thereby optimizing long-term treatment outcomes for patients. The study aimed to review the existing data on tyrosine kinase inhibitors and their potential ototoxicity, including the main mechanisms of pathogenesis. Methods: The search utilized PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar, and ClinicalTrials.gov to identify scientific publications on ototoxicity caused by TKIs in NSCLC. The keywords “non-small cell lung cancer,” “ototoxicity,” “gefitinib,” “erlotinib,” “afatinib,” “dacomitinib,” and “osimertinib” were used for the search. Results: EGFR plays an important role in developing, maintaining, and repairing sensory and non-sensory structures of the inner ear. In neonatal models, EGFR is expressed in cochlear cells, including the cortical organ, facilitating regeneration and repair. However, in mature systems, EGFR expression decreases, primarily localized in the spiral ganglion, limiting the regenerative ability of auditory cells. By inhibiting EGFR signaling, cellular proliferation and repair mechanisms are disrupted, damaging the cochlea’s hair cells and supporting cells. Conclusion: The prevalence and main molecular mechanisms of ototoxicity caused by TKI remain poorly understood. Further research is needed to clarify dose-dependent effects, genetic predisposition, and potential protective strategies. Knowledge of this adverse effect is necessary to monitor auditory health during EGFR-TKI therapy and to study interventions that mitigate its effects on patients undergoing long-term treatment.