Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated cardiovascular toxicities.
Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated cardiovascular toxicities.
复制标题
酪氨酸激酶抑制剂相关的心血管毒性的机制，监测和管理。
DOI：
10.2147/ott.s170138
复制
发表时间：
2018
影响因子：
4
通讯作者：
Ait-Oudhia S
中科院分区：
文献类型：
--
作者：
Chaar M;Kamta J;Ait-Oudhia S
酪氨酸激酶抑制剂（TKI）药物类别是治疗各种癌症的主要选择。对这些药物的安全性评价显示，有证据表明，不同药物之间存在不同频率和严重程度的心脏毒性;对这一问题的关注导致更新了标签，警告处方者。本综述旨在澄清目前的危险，并调查心脏毒性的作用机制，为每一个讨论的TKI。在临床研究中，达沙替尼主要与液体潴留、水肿、QT间期延长和肺动脉高压的发生有关。理论上，这是由于Bcr-Abl的脱靶激酶结合和中靶结合的组合，并且不太可能是线粒体诱导的细胞凋亡。研究表明索拉非尼有高血压、QT间期延长和心肌梗死的风险。提出的这些副作用的机制包括抑制蛋白质、血管内皮生长因子受体、hERG钾通道和RAF/MERK/ERK促存活通路。最后，拉帕替尼在临床研究中显示了左心室射血分数（LVEF）降低和QT间期延长的证据。文献将这些归因于靶向ErbB 2结合导致线粒体诱导的细胞凋亡的副作用。这些调查结果所引起的关注值得商榷。汇总的安全性数据表明，达沙替尼和拉帕替尼的心脏毒性总体风险极小。索拉非尼似乎有适度的担忧。对于讨论的药物，建议同意在治疗过程中通过脑电图，心脏生物标志物和血压等方法进行常规监测，此外还需要全面收集既往病史和风险因素，以确定心血管事件风险增加的患者。
The tyrosine kinase inhibitor (TKI) drug class is a prominently used option in the treatment of various cancers. Safety evaluation of these drugs has shown evidence of cardiotoxicity of varying frequency and severity between agents; concern has led to updated labeling, warning prescribers of such. This review seeks to clarify the present dangers and investigate cardiotoxic mechanisms of action for each discussed TKI. Dasatinib was connected primarily with an incidence of fluid retention, edema, QT prolongation, and pulmonary hypertension in clinical studies. It is theorized that this is due to a combination of off-target kinase binding and on-target binding of Bcr-Abl, and less likely, mitochondrial induced apoptosis. Studies showed sorafenib to carry the risk of hypertension, QT prolongation, and myocardial infarction. Proposed mechanisms for these side effects include inhibition of proteins, vascular endothelium growth factor receptor, hERG potassium channels, and the RAF/MERK/ERK pro-survival pathway. Finally, lapatinib showed evidence of decreased left ventricular ejection fraction (LVEF) and QT prolongation in clinical studies. The literature attributes these as side effects of on-target ErbB2 binding leading to mitochondrial induced apoptosis. The concern warranted by these findings is in question. Pooled safety data suggest that the overall risk for cardiotoxicity is minimal in dasatinib and lapatinib. Sorafenib seems to carry a moderate concern. For the discussed agents, recommendations agree that routine monitoring via methods such as electroencephalogram, cardiac biomarkers, and blood pressure is warranted during the course of treatment, in addition to a comprehensive collection of past medical history and risk factors to identify those at heightened risk for cardiovascular events.
达沙替尼在费城染色体阴性白血病和髓样疾病的临床前和临床经验。
影响因子：
2.7
作者：
Verstovsek S
通讯作者：
Verstovsek S