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精准心脏肿瘤学:酪氨酸激酶抑制剂和免疫检查点抑制剂心脏毒性的系统视角。

Precision Cardio-Oncology: a Systems-Based Perspective on Cardiotoxicity of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.

机构信息

Department of Cardiovascular Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.

出版信息

J Cardiovasc Transl Res. 2020 Jun;13(3):402-416. doi: 10.1007/s12265-020-09992-5. Epub 2020 Apr 6.

Abstract

Cancer therapies have been evolving from conventional chemotherapeutics to targeted agents. This has fulfilled the hope of greater efficacy but unfortunately not of greater safety. In fact, a broad spectrum of toxicities can be seen with targeted therapies, including cardiovascular toxicities. Among these, cardiomyopathy and heart failure have received greatest attention, given their profound implications for continuation of cancer therapies and cardiovascular morbidity and mortality. Prediction of risk has always posed a challenge and even more so with the newer targeted agents. The merits of accurate risk prediction, however, are very evident, e.g. facilitating treatment decisions even before the first dose is given. This is important for agents with a long half-life and high potential to induced life-threatening cardiac complications, such as myocarditis with immune checkpoint inhibitors. An opportunity to address these needs in the field of cardio-oncology is provided by the expanding repertoire of "-omics" and other tools in precision medicine and their integration in a systems biology approach. This may allow for new insights into patho-mechanisms and the creation of more precise and cost-effective risk prediction tools with the ultimate goals of improved therapy decisions and prevention of cardiovascular complications. Herein, we explore this topic as a future approach to translating the complexity of cardio-oncology to the reality of patient care.

摘要

癌症治疗方法已经从传统的化疗药物发展为靶向药物。这一发展实现了提高疗效的希望,但不幸的是,并没有提高安全性。事实上,靶向治疗会引起广泛的毒性,包括心血管毒性。在这些毒性中,心肌病和心力衰竭受到了最大的关注,因为它们对癌症治疗的继续进行以及心血管发病率和死亡率有深远的影响。风险预测一直是一个挑战,对于新型靶向药物更是如此。然而,准确风险预测的好处是非常明显的,例如,即使在给予第一剂药物之前,也可以帮助做出治疗决策。对于半衰期长且有高风险引发危及生命的心脏并发症的药物,如免疫检查点抑制剂引起的心肌炎,这一点尤其重要。精准医学中的“组学”和其他工具的扩展以及它们在系统生物学方法中的整合,为心脏肿瘤学领域提供了一个解决这些需求的机会。这可能会为病理机制提供新的见解,并创建更精确和更具成本效益的风险预测工具,最终目标是改善治疗决策和预防心血管并发症。在此,我们探讨了这一主题,将心脏肿瘤学的复杂性转化为患者护理的现实。

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