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Review
. 2019 Jun 7;40(22):1764-1770.
doi: 10.1093/eurheartj/ehx811.

Cancer therapy-induced cardiomyopathy: can human induced pluripotent stem cell modelling help prevent it?

Jonathan P Stack  1   2   3   4 , Javid Moslehi  5   6 , Nazish Sayed  1   2   3 , Joseph C Wu  1   2   3
Affiliations
Review

Cancer therapy-induced cardiomyopathy: can human induced pluripotent stem cell modelling help prevent it?

Jonathan P Stack et al. Eur Heart J. .

Abstract

Cardiotoxic effects from cancer therapy are a major cause of morbidity during cancer treatment. Unexpected toxicity can occur during treatment and/or after completion of therapy, into the time of cancer survivorship. While older drugs such as anthracyclines have well-known cardiotoxic effects, newer drugs such as tyrosine kinase inhibitors, proteasome inhibitors, and immunotherapies also can cause diverse cardiovascular and metabolic complications. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly being used as instruments for disease modelling, drug discovery, and mechanistic toxicity studies. Promising results with hiPSC-CM chemotherapy studies are raising hopes for improving cancer therapies through personalized medicine and safer drug development. Here, we review the cardiotoxicity profiles of common chemotherapeutic agents as well as efforts to model them in vitro using hiPSC-CMs.

Keywords: Cardio-oncology; Chemotherapy; Genomics; Induced pluripotent stem cells; Precision medicine.

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Figures

Figure 1
Figure 1
(A) Traditional chemotherapeutics non-specifically target malignant cells, causing impairment of mitotic processes such as microtubule formation, cellular damage, or direct DNA damage and ROS generation. (B) Targeted cancer therapies target pathways or proteins unique to cancer cells or essential for their survival. ROS, reactive oxygen species.
Figure 2
Figure 2
Future chemotherapy protocols may involve a combination of rational drug selection based on human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) screening as well as monitoring for the earliest signs of toxicity through advanced imaging techniques and cardiac biomarkers.
Figure 3
Figure 3
For drug development, human induced pluripotent stem cell-derived cells or tissues can be used to screen for uncommon or rare toxic reactions before beginning clinical testing. Unsafe drug candidates can be removed from the testing pool instead of progressing to clinical trials.
See this image and copyright information in PMC

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