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Human In Vitro Models for Assessing the Genomic Basis of Chemotherapy-Induced Cardiovascular Toxicity

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Abstract

Chemotherapy-induced cardiovascular toxicity (CICT) is a well-established risk for cancer survivors and causes diseases such as heart failure, arrhythmia, vascular dysfunction, and atherosclerosis. As our knowledge of the precise cardiovascular risks of each chemotherapy agent has improved, it has become clear that genomics is one of the most influential predictors of which patients will experience cardiovascular toxicity. Most recently, GWAS-led, top-down approaches have identified novel genetic variants and their related genes that are statistically related to CICT. Importantly, the advent of human-induced pluripotent stem cell (hiPSC) models provides a system to experimentally test the effect of these genomic findings in vitro, query the underlying mechanisms, and develop novel strategies to mitigate the cardiovascular toxicity liabilities due to these mechanisms. Here we review the cardiovascular toxicities of chemotherapy drugs, discuss how these can be modeled in vitro, and suggest how these models can be used to validate genetic variants that predispose patients to these effects.

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Funding

This study was funded by NIH NCI grant R01 CA220002, American Heart Association Transformational Project Award 18TPA34230105 and the Fondation Leducq (P.W.B).

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Authors and Affiliations

  1. Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Emily A. Pinheiro, Tarek Magdy & Paul W. Burridge

  2. Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Emily A. Pinheiro, Tarek Magdy & Paul W. Burridge

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  1. Emily A. Pinheiro
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  2. Tarek Magdy
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Correspondence to Paul W. Burridge.

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Pinheiro, E.A., Magdy, T. & Burridge, P.W. Human In Vitro Models for Assessing the Genomic Basis of Chemotherapy-Induced Cardiovascular Toxicity. J. of Cardiovasc. Trans. Res. 13, 377–389 (2020). https://doi.org/10.1007/s12265-020-09962-x

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