Preclinical Models of Cancer Therapy-Associated Cardiovascular Toxicity: A Scientific Statement from the American Heart Association

Aarti Asnani, Javid J. Moslehi, Bishow B. Adhikari, Alan H. Baik, Andreas M. Beyer, Rudolf A. De Boer, Alessandra Ghigo, Isabella M. Grumbach, Salvia Jain, Han Zhu

Research output: Contribution to journalReview articleAcademicpeer-review

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)E21-E34
JournalCirculation Research
Volume129
Issue number1
DOIs
Publication statusPublished - 25 Jun 2021
Externally publishedYes

Bibliographical note

Funding Information:
Abcuro, Inc. (research funding was obtained from company)†; NCI (K08 Career Development Grant was obtained)†

Funding Information:
NIH (research grant to study vas cular toxicity)†

Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.

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