曲妥珠单抗
心脏毒性
自噬
氧化应激
医学
ULK1
药理学
PI3K/AKT/mTOR通路
癌症研究
信号转导
内科学
细胞凋亡
毒性
癌症
化学
生物
乳腺癌
细胞生物学
蛋白激酶A
激酶
生物化学
安普克
作者
Nishant Mohan,Junjie Jiang,Wen Jin Wu
出处
期刊:PubMed
日期:2017-01-01
卷期号:2 (1)
被引量:19
摘要
Trastuzumab, a humanized monoclonal antibody directed against human epidermal growth factor receptor 2 (HER2), remains the standard of care as part of adjuvant therapy for patients diagnosed with HER2-positive breast cancers. Despite high therapeutic efficacy, trastuzumab-based regimens can cause serious cardiotoxic side effects. Effective mitigation of cardiotoxic risk relies on thorough understanding of molecular mechanisms of cardiotoxicity induced by trastuzumab. Among the probable mechanisms responsible for trastuzumab-mediated cardiotoxicity, generation of free radicals causing oxidative stress has garnered notable attention in recent years. More recently, role of autophagy in trastuzumab-induced cardiomyopathy was explored. Trastuzumab-mediated HER2 signaling dysregulation activated Erk/mTOR signaling cascade resulting in autophagy inhibition. Consequently, autophagy impairment leads to massive accumulation of damaged mitochondria and free radicals causing oxidative stress and toxicity in cardiomyocytes. This review will discuss recent advances in understanding the mechanism of oxidative stress and highlight the role of autophagy in trastuzumab-mediated cardiac dysfunctions.
科研通智能强力驱动
Strongly Powered by AbleSci AI