Yang ZiYan, Wang Wei, Wang Xiaojia, Qin ZhiQuan
Department of Oncology Center, Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
Graduate School of Bengbu Medical College, Bengbu, China.
Front Pharmacol. 2021 Nov 1;12:741451. doi: 10.3389/fphar.2021.741451. eCollection 2021.
Breast cancer is the most common form of cancer in women and its incidence has been increasing over the years. Human epidermal growth factor receptor 2 (HER2 or ErbB2) overexpression is responsible for 20 to 25% of invasive breast cancers, and is associated with poor prognosis. HER2-targeted therapy has significantly improved overall survival rates in patients with HER2-positive breast cancer. However, despite the benefits of this therapy, its cardiotoxicity is a major concern, especially when HER2-targeted therapy is used in conjunction with anthracyclines. At present, the mechanism of this cardiotoxicity is not fully understood. It is thought that HER2-targeting drugs inhibit HER2/NRG 1 dimer formation, causing an increase in ROS in the mitochondria of cardiomyocytes and inhibiting the PI3K/Akt and Ras/MAPK pathways, resulting in cell apoptosis. Antioxidants, ACE inhibitors, angiotensin II receptor blockers, β-blockers, statins and other drugs may have a cardioprotective effect when used with ErbB2-targeting drugs. NT-proBNP can be used to monitor trastuzumab-induced cardiotoxicity during HER2-targeted treatment and may serve as a biological marker for clinical prediction of cardiotoxicity. Measuring NT-proBNP is non-invasive, inexpensive and reproducible, therefore is worthy of the attention of clinicians. The aim of this review is to discuss the potential mechanisms, clinical features, diagnostic strategies, and intervention strategies related to cardiotoxicity of ErbB2-targeting drugs.
乳腺癌是女性中最常见的癌症形式,并且其发病率多年来一直在上升。人表皮生长因子受体2(HER2或ErbB2)过表达导致20%至25%的浸润性乳腺癌,并且与预后不良相关。HER2靶向治疗显著提高了HER2阳性乳腺癌患者的总生存率。然而,尽管这种治疗有诸多益处,但其心脏毒性是一个主要问题,尤其是当HER2靶向治疗与蒽环类药物联合使用时。目前,这种心脏毒性的机制尚未完全明确。据认为,HER2靶向药物抑制HER2/NRG 1二聚体形成,导致心肌细胞线粒体中活性氧增加,并抑制PI3K/Akt和Ras/MAPK途径,从而导致细胞凋亡。抗氧化剂、血管紧张素转换酶抑制剂、血管紧张素II受体阻滞剂、β受体阻滞剂、他汀类药物和其他药物与ErbB2靶向药物联合使用时可能具有心脏保护作用。NT-proBNP可用于监测HER2靶向治疗期间曲妥珠单抗诱导的心脏毒性,并可作为心脏毒性临床预测的生物标志物。检测NT-proBNP是非侵入性的、廉价的且可重复的,因此值得临床医生关注。本综述的目的是讨论与ErbB2靶向药物心脏毒性相关的潜在机制、临床特征、诊断策略和干预策略。