Research progress of cardiotoxicity related to the third generation of epidermal growth factor receptor-tyrosine kinase inhibitors
陈昇 1万畅 1张以若 1康彦红
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作者信息
1. 安徽医科大学第一附属医院肿瘤内科，合肥 230022
折叠
摘要
奥希替尼（osimertinib）、阿美替尼（almonertinib）和伏美替尼（furmonertinib）等第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）是EGFR基因突变晚期非小细胞肺癌的重要治疗手段，其心脏毒性不容忽视。目前发现的该类药物的心脏毒性以校正的QT间期延长为主，其次可见左心室射血分数下降和心力衰竭。这些心脏毒性症状可单独出现，也可同时发生。第三代EGFR-TKI心脏毒性的相关机制尚不明确，可能与抑制人表皮生长因子受体-2（HER-2）信号通路、磷脂酰肌醇3-激酶（PI3K）/Akt通路、hERG钾通道（即由hERG基因编码的钾离子通道）、电压门控钠离子通道（Nav1.5）和L型钙离子通道等相关。临床需谨慎应用第三代EGFR-TKI，提前识别心脏毒性高风险人群并做好治疗药物监测。 The third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as osimertinib, almonertinib, and furmonertinib, played a crucial role in the treatment of advanced non-small cell lung cancer with EGFR gene mutations. However, it was essential to consider their potential cardiotoxicity. Currently, the primary cardiotoxicity associated with this kind of drugs was prolongation of the corrected QT interval, followed by decline in left ventricular ejection fraction and heart failure. These manifestations could occur independently or concurrently. The underlying mechanism responsible for the cardiotoxicity of the third generation EGFR-TKIs remained unknown but might be attributed to inhibition of the human epidermal growth factor receptor 2 (HER-2) signal pathway, suppression of the phosphoinositide 3-kinase (PI3K)/Akt pathway, blockade of the human ether-à-go-go-related gene (hERG) potassium channel, inhibition of the voltage-gated sodium channel (Nav1.5), and modulation of the L-type calcium channel. Therefore, caution should be exercised when using the third generation EGFR-TKIs clinically by promptly identifying high-risk individuals susceptible to cardiotoxicity and closely conducting therapeutic drug monitoring.
Abstract
The third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as osimertinib, almonertinib, and furmonertinib, played a crucial role in the treatment of advanced non-small cell lung cancer with EGFR gene mutations. However, it was essential to consider their potential cardiotoxicity. Currently, the primary cardiotoxicity associated with this kind of drugs was prolongation of the corrected QT interval, followed by decline in left ventricular ejection fraction and heart failure. These manifestations could occur independently or concurrently. The underlying mechanism responsible for the cardiotoxicity of the third generation EGFR-TKIs remained unknown but might be attributed to inhibition of the human epidermal growth factor receptor 2 (HER-2) signal pathway, suppression of the phosphoinositide 3-kinase (PI3K)/Akt pathway, blockade of the human ether-à-go-go-related gene (hERG) potassium channel, inhibition of the voltage-gated sodium channel (Nav1.5), and modulation of the L-type calcium channel. Therefore, caution should be exercised when using the third generation EGFR-TKIs clinically by promptly identifying high-risk individuals susceptible to cardiotoxicity and closely conducting therapeutic drug monitoring.
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