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Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK-inhibitors
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2018-06-28 , DOI: 10.1016/j.pharmthera.2018.06.017
Enrico Bronte , Giuseppe Bronte , Giuseppina Novo , Gaetana Rinaldi , Fabrizio Bronte , Francesco Passiglia , Antonio Russo

Many new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on hypertension and ejection fraction reduction development. Then, it follows the examination of published data for each combination therapy. A Literature research was carried out using Pubmed selecting review articles, original studies and clinical trials, but mainly focusing on phase 3 studies. This work aims to summarize the knowledge about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity to make it usable and give the basic tools to Cardiologists and Oncologists for a better management of cancer patient undergoing this treatment. Besides a deeper knowledge of the cardiovascular adverse events linked to this treatment and the magnitude of their expression and frequency can lead to a targeted cardiological treatment.



中文翻译:

BRAF抑制剂和MEK抑制剂组合的心脏毒性机制

近年来,在肿瘤治疗中出现了许多新药。每种药物都带有一系列重要的不良事件,不少于心血管不良事件。考虑到在某些正在进行的临床试验中,越来越多地使用两种药物或三种药物的联合疗法,这一方面就显得尤为重要。除此之外,它对心脏病专家来说是一个日益严重的问题,它在日常临床实践中都面临着这个问题,并且在未来几年中可能会越来越多地面临它。这项工作审查了BRAF抑制剂和MEK抑制剂一起使用的作用机理,导致心血管毒性的病理生理机制。特别地,它着重于高血压和射血分数降低的发展。然后,检查每种联合疗法的公开数据。使用Pubmed选择评论文章,原始研究和临床试验进行了文献研究,但主要侧重于3期研究。这项工作旨在总结有关BRAF抑制剂和MEK抑制剂治疗的知识及其心血管毒性,使其有用,并为心脏病专家和肿瘤科医生提供基础工具,以更好地管理接受该治疗的癌症患者。除了对与这种治疗有关的心血管不良事件及其表达和频率的大小有更深入的了解外,还可以导致有针对性的心脏病治疗。这项工作旨在总结有关BRAF抑制剂和MEK抑制剂治疗的知识及其心血管毒性,使其有用,并为心脏病专家和肿瘤科医生提供基础工具,以更好地管理接受该治疗的癌症患者。除了对与这种治疗有关的心血管不良事件及其表达和频率的大小有更深入的了解外,还可以导致有针对性的心脏病治疗。这项工作旨在总结有关BRAF抑制剂和MEK抑制剂治疗的知识及其心血管毒性,使其有用,并为心脏病专家和肿瘤科医生提供基本工具,以更好地管理接受该治疗的癌症患者。除了对与这种治疗有关的心血管不良事件及其表达和频率的大小有更深入的了解外,还可以导致有针对性的心脏病治疗。

更新日期:2018-06-28
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