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Published on: June 7, 2018
Zebrafish Models of Cancer Therapy-Induced Cardiovascular Toxicity
Sarah Lane1, Luis Alberto More1, Aarti Asnani1,2
1CardioVascular Institute, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
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.
Insights
Zebrafish models effectively study cancer therapy cardiotoxicity, identifying protective strategies without compromising antitumor effects. Genetic conservation and recapitulated phenotypes make them valuable, despite developmental stage limitations.
Area of Science:
- Cardiovascular Biology
- Oncology
- Toxicology
- Zebrafish Models
Background:
- Cancer therapies, both traditional and novel, can induce cardiovascular toxicity.
- Understanding on- and off-target mechanisms of toxicity requires integrated in vivo models.
- Zebrafish offer a unique whole-organism platform for high-throughput screening of cardiotoxicity.
Purpose of the Study:
- To review established zebrafish models for cardiovascular disease and cancer.
- To highlight zebrafish advantages in studying cancer therapy-associated cardiovascular toxicity mechanisms.
- To discuss limitations of zebrafish models in toxicity studies.
Main Methods:
- Utilizing established zebrafish models of human cardiovascular disease and cancer.
- Employing high-throughput screening to assess cardiotoxicity.
- Leveraging transgenic zebrafish lines created via genome editing.
Main Results:
- Zebrafish models can identify novel therapies protecting the heart from cancer treatment toxicity.
- These models help assess impacts on antitumor activity.
- Transgenic zebrafish lines aid in studying cardiovascular and cancer pathophysiology.
Conclusions:
- Zebrafish models effectively recapitulate human cancer therapy-associated cardiovascular toxicity phenotypes.
- High genetic conservation with humans enhances model relevance.
- Limitations include the early developmental stages needed for high-throughput studies.
