Preclinical Models of Cancer Therapy-Associated Cardiovascular Toxicity: A Scientific Statement From the American Heart Association.
Preclinical Models of Cancer Therapy-Associated Cardiovascular Toxicity: A Scientific Statement From the American Heart Association.
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DOI：
10.1161/res.0000000000000473
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发表时间：
2021-06-25
影响因子：
20.1
通讯作者：
American Heart Association Council on Basic Cardiovascular Sciences; Cardio-Oncology Science Subcommittee of Council on Genomic and Precision Medicine and Council on Clinical Cardiology; Council on Peripheral Vascular Disease; and Council on Arteriosclerosis, Thrombosis and Vascular Biology
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文献类型：
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作者：
Asnani A;Moslehi JJ;Adhikari BB;Baik AH;Beyer AM;de Boer RA;Ghigo A;Grumbach IM;Jain S;Zhu H;American Heart Association Council on Basic Cardiovascular Sciences; Cardio-Oncology Science Subcommittee of Council on Genomic and Precision Medicine and Council on Clinical Cardiology; Council on Peripheral Vascular Disease; and Council on Arteriosclerosis, Thrombosis and Vascular Biology
虽然传统化疗的心血管毒性已经被公认了几十年，但最近爆发的有效的新型靶向癌症治疗与心血管后遗症已经推动了心脏肿瘤学作为一个新的临床和研究领域的出现。与癌症治疗相关的心血管毒性可表现为广泛的潜在危及生命的并发症，包括心力衰竭、心律失常、心肌炎和血管事件。除了毒理学，癌症和心脏病的交叉点已经发展到包括发现易患两者的遗传和环境风险因素。迫切需要了解心血管毒性的潜在分子机制，以改善癌症患者的预后。临床前心血管模型，从细胞测定到大型动物，是机制研究的基础，最终目标是确定生物学上合理的生物标志物和心脏保护疗法，使癌症治疗的最佳使用，同时最大限度地减少毒性。鉴于新型癌症疗法针对正常心血管稳态不可或缺的特定途径，对毒性的更好机制理解可能会提供对调节失调时导致心血管疾病的基本途径的见解。本科学声明的目的是总结癌症治疗相关心血管毒性的临床前模型的优点和缺点，强调驱动癌症和心血管疾病的重叠机制，并讨论利用心脏肿瘤学模型来解决与所有心血管疾病患者相关的重要机制问题的机会，包括那些患有和没有癌症的患者。
Although cardiovascular toxicity from traditional chemotherapies has been well recognized for decades, the recent explosion of effective novel targeted cancer therapies with cardiovascular sequelae has driven the emergence of cardio-oncology as a new clinical and research field. Cardiovascular toxicity associated with cancer therapy can manifest as a broad range of potentially life-threatening complications, including heart failure, arrhythmia, myocarditis, and vascular events. Beyond toxicology, the intersection of cancer and heart disease has blossomed to include discovery of genetic and environmental risk factors that predispose to both. There is a pressing need to understand the underlying molecular mechanisms of cardiovascular toxicity to improve outcomes in patients with cancer. Preclinical cardiovascular models, ranging from cellular assays to large animals, serve as the foundation for mechanistic studies, with the ultimate goal of identifying biologically sound biomarkers and cardioprotective therapies that allow the optimal use of cancer treatments while minimizing toxicities. Given that novel cancer therapies target specific pathways integral to normal cardiovascular homeostasis, a better mechanistic understanding of toxicity may provide insights into fundamental pathways that lead to cardiovascular disease when dysregulated. The goal of this scientific statement is to summarize the strengths and weaknesses of preclinical models of cancer therapy–associated cardiovascular toxicity, to highlight overlapping mechanisms driving cancer and cardiovascular disease, and to discuss opportunities to leverage cardio-oncology models to address important mechanistic questions relevant to all patients with cardiovascular disease, including those with and without cancer.