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针对抗癌治疗引起的心脏毒性靶向G蛋白偶联受体

Targeting GPCRs Against Cardiotoxicity Induced by Anticancer Treatments.

作者信息

Audebrand Anais, Désaubry Laurent, Nebigil Canan G

机构信息

Laboratory of CardioOncology and Therapeutic Innovation, CNRS, Illkirch, France.

出版信息

Front Cardiovasc Med. 2020 Jan 24;6:194. doi: 10.3389/fcvm.2019.00194. eCollection 2019.

Abstract

Novel anticancer medicines, including targeted therapies and immune checkpoint inhibitors, have greatly improved the management of cancers. However, both conventional and new anticancer treatments induce cardiac adverse effects, which remain a critical issue in clinic. Cardiotoxicity induced by anti-cancer treatments compromise vasospastic and thromboembolic ischemia, dysrhythmia, hypertension, myocarditis, and cardiac dysfunction that can result in heart failure. Importantly, none of the strategies to prevent cardiotoxicity from anticancer therapies is completely safe and satisfactory. Certain clinically used cardioprotective drugs can even contribute to cancer induction. Since G protein coupled receptors (GPCRs) are target of forty percent of clinically used drugs, here we discuss the newly identified cardioprotective agents that bind GPCRs of adrenalin, adenosine, melatonin, ghrelin, galanin, apelin, prokineticin and cannabidiol. We hope to provoke further drug development studies considering these GPCRs as potential targets to be translated to treatment of human heart failure induced by anticancer drugs.

摘要

包括靶向疗法和免疫检查点抑制剂在内的新型抗癌药物极大地改善了癌症的治疗。然而,传统和新型抗癌治疗都会引发心脏不良反应,这在临床上仍然是一个关键问题。抗癌治疗引起的心脏毒性会导致血管痉挛和血栓栓塞性缺血、心律失常、高血压、心肌炎以及可能导致心力衰竭的心脏功能障碍。重要的是,预防抗癌治疗引起心脏毒性的策略都不完全安全且令人满意。某些临床使用的心脏保护药物甚至可能导致癌症发生。由于G蛋白偶联受体(GPCRs)是40%临床使用药物的靶点,在此我们讨论新发现的与肾上腺素、腺苷、褪黑素、胃饥饿素、甘丙肽、阿片肽、促动力蛋白和大麻二酚的GPCRs结合的心脏保护剂。我们希望激发进一步的药物开发研究,将这些GPCRs视为潜在靶点,用于转化治疗抗癌药物引起的人类心力衰竭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7b0/6993588/68680114284c/fcvm-06-00194-g0001.jpg

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