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BRAF与心脏功能有何关联?BRAF抑制剂在癌症治疗中的心脏毒性带来的新见解。

What links BRAF to the heart function? New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment.

作者信息

Bronte Enrico, Bronte Giuseppe, Novo Giuseppina, Bronte Fabrizio, Bavetta Maria Grazia, Lo Re Giuseppe, Brancatelli Giuseppe, Bazan Viviana, Natoli Clara, Novo Salvatore, Russo Antonio

机构信息

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

Department of Internal Medicine and Cardiovascular Disease, University of Palermo, Palermo, Italy.

出版信息

Oncotarget. 2015 Nov 3;6(34):35589-601. doi: 10.18632/oncotarget.5853.

Abstract

The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation.

摘要

RAS相关信号级联在细胞中具有重要作用。它激活细胞分化和存活。其分子之一B-RAF尤为重要。B-RAF一直是研究的核心点,尤其是在黑色素瘤方面。事实上,自其研究早期以来就缺乏有效的治疗手段。针对B-RAF的分子已被研发出来。如今,两类分子已获美国食品药品监督管理局(FDA)批准。多靶点分子,如索拉非尼和瑞戈非尼,以及选择性分子,如维莫非尼和达拉非尼。许多其他分子仍在研究中。其中大多数处于1期试验阶段。临床研究将B-RAF抑制剂与QT间期延长相关联。尽管使用这些药物时这种心血管副作用并不常见,但必须尽早注意并识别其信号。实际上,肿瘤学家和心脏病学家应合作预防致命事件,如致命性心律失常或心源性猝死。这些事件可能源于不受控制的QT间期延长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6069/4742127/285ea50e1e84/oncotarget-06-35589-g001.jpg

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