Molecular mechanisms of lung-specific toxicity induced by epidermal growth factor receptor tyrosine kinase inhibitors

Abstract

Lung-specific toxicity induced by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of non-small cell lung cancer (NSCLC) has emerged as a critical side-effect. Although the clinical features of the pulmonary side-effects of TKIs have been characterized, the details of the molecular mechanisms in the development of this lung-specific toxicity remain to be elucidated. EGFR-dependent epithelial regeneration and restoration plays an important role in the recovery process from lung injury. The lung comprises a unique environment where epithelial cells are exposed to internal agents in the systemic circulation and to airborne particles through the mouth and nose. This unique environment may also be associated with the development of lung-specific toxicity induced by EGFR-TKIs. Therefore, the aim of this review was to provide further insight into the molecular mechanisms of lung-specific toxicity in the context of treatment with EGFR-TKIs.