Abstract
Purpose of review: Both traditional and novel cancer therapies can cause cardiovascular toxicity in patients. In vivo models integrating both cardiovascular and cancer phenotypes allow for the study of on- and off-target mechanisms of toxicity arising from these agents. The zebrafish is the optimal whole organism model to screen for cardiotoxicity in a high throughput manner, while simultaneously assessing the role of cardiotoxicity pathways on the cancer therapy’s antitumor effect. Here we highlight established zebrafish models of human cardiovascular disease and cancer, the unique advantages of zebrafish to study mechanisms of cancer therapy-associated cardiovascular toxicity, and finally, important limitations to consider when using the zebrafish to study toxicity. Recent findings: Cancer therapy-associated cardiovascular toxicities range from cardiomyopathy with traditional agents to arrhythmias and thrombotic complications associated with newer targeted therapies. The zebrafish can be used to identify novel therapeutic strategies that selectively protect the heart from cancer therapy without affecting antitumor activity. Advances in genome editing technology have enabled the creation of several transgenic zebrafish lines valuable to the study of cardiovascular and cancer pathophysiology. Summary: The high degree of genetic conservation between zebrafish and humans, as well as the ability to recapitulate cardiotoxic phenotypes observed in patients with cancer, make the zebrafish an effective model to study cancer therapy-associated cardiovascular toxicity. Though this model provides several key benefits over existing in vitro and in vivo models, limitations of the zebrafish model include the early developmental stage required for most high-throughput applications.
Highlights
Cardiovascular disease and cancer are leading causes of morbidity and mortality worldwide
Even though modern cancer treatment strategies have led to higher cancer survivorship rates, many regimens used currently are associated with cancer therapy-induced cardiovascular toxicity [3]
In a large cohort of patients treated with anthracyclines, the incidence of cardiac dysfunction was 9% within the first year after completion of treatment [4], with higher rates of cardiomyopathy reported in patients with pre-existing cardiovascular disease
Summary
Cardiovascular disease and cancer are leading causes of morbidity and mortality worldwide. In a large cohort of patients treated with anthracyclines, the incidence of cardiac dysfunction was 9% within the first year after completion of treatment [4], with higher rates of cardiomyopathy reported in patients with pre-existing cardiovascular disease. The ability to use zebrafish to study both cardiovascular diseases and cancer, along with the advantages of performing high throughput discovery studies, makes the zebrafish a desirable model for cancer therapy-associated cardiotoxicity. Models that recapitulate cancer therapy-associated cardiovascular toxicity have successfully been developed and have the potential to provide new insights into fundamental cardiovascular biology outside the context of cancer. This review addresses zebrafish as a model for cancer therapy-induced cardiovascular toxicity, emphasizing the role of zebrafish in studying both cardiovascular diseases and cancer biology for a comprehensive assessment of chemotherapy-induced cardiotoxicity
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