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抗癌药物所致心脏毒性的体内小鼠模型:临床转化的挑战与机遇。

In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation.

机构信息

Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.

Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

出版信息

J Cardiovasc Transl Res. 2022 Oct;15(5):1143-1162. doi: 10.1007/s12265-022-10231-2. Epub 2022 Mar 21.

Abstract

Modern therapeutic approaches have led to an improvement in the chances of surviving a diagnosis of cancer. However, this may come with side effects, with patients experiencing adverse cardiovascular events or exacerbation of underlying cardiovascular disease related to their cancer treatment. Rodent models of chemotherapy-induced cardiotoxicity are useful to define pathophysiological mechanisms of cardiac damage and to identify potential therapeutic targets. The key mechanisms involved in cardiotoxicity induced by specific different antineoplastic agents are summarized in this state-of-the-art review, as well as the rodent models of cardiotoxicity by different classes of anticancer drugs, along with the strategies tested for primary and secondary cardioprotection. Current approaches for early detection of cardiotoxicity in preclinical studies with a focus on the application of advanced imaging modalities and biomarker strategies are also discussed. Potential applications of cardiotoxicity modelling in rodents are illustrated in relation to the advancements of promising research topics of cardiotoxicity. Created with BioRender.com.

摘要

现代治疗方法提高了癌症诊断后的生存机会。然而,这可能伴随着副作用,患者会出现不良心血管事件或癌症治疗相关的潜在心血管疾病恶化。化疗诱导性心脏毒性的啮齿动物模型有助于明确心脏损伤的病理生理机制,并确定潜在的治疗靶点。本文综述了不同抗肿瘤药物引起心脏毒性的关键机制,以及不同类别的抗肿瘤药物引起心脏毒性的啮齿动物模型,同时还介绍了用于一级和二级心脏保护的策略。本文还讨论了目前在临床前研究中早期检测心脏毒性的方法,重点是应用先进的成像方式和生物标志物策略。本文还举例说明了心脏毒性建模在与心脏毒性有希望的研究主题进展相关的啮齿动物中的潜在应用。使用 BioRender.com 创建。

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