奥希替尼相关心脏毒性的研究进展

Research progress in osimertinib-related cardiotoxicity

奥希替尼是一种作用于表皮生长因子受体(epidermal growth factor receptor,EGFR)的第三代酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI),主要用于治疗EGFR突变的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者。心脏毒性是奥希替尼常见的不良反应之一,其发生机制可能与奥希替尼抑制磷脂酰肌醇激酶3(phosphoinositide 3-kinase,PI3K)信号通路或人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER^(2))/神经调节蛋白1(neuregulin 1,NRG1)信号通路相关;临床表现主要为QT间期延长(QT interval prolongation,QTIP)、左心室射血分数(left ventricular ejection fraction,LVEF)降低和心力衰竭(heart failure,HF),严重时可危及患者生命;其发生的危险因素涉及心脏疾病史和联合用药。奥希替尼治疗时应对患者进行心功能监测,以便及时发现和干预可能发生的心脏毒性。

Osimertinib is a third-generation tyrosine kinase inhibitor(TKI),which can act on epidermal growth factor receptor(EGFR).It is mainly used for the treatment of advanced non-small cell lung cancer(NSCLC) patients with EGFR mutations.Cardiotoxicity is one of the common adverse reactions of osimertinib,which may be related to the inhibition of phosphoinositide 3-kinase(PI3K) signaling pathway or human epidermal growth factor receptor 2(HER^(2))/neuregulin 1(NRG1) signaling pathway by osimertinib.The main clinical manifestations are QT interval prolongation(QTIP),left ventricular ejection fraction(LVEF) decrease and heart failure(HF),which endanger the patient's life in severe cases.The risk factors involved are history of heart disease and drug combination.Cardiac function monitoring should be performed during osimertinib therapy in order to detect and intervene the possible cardiotoxicity in time.