Top Things to Know: Preclinical Models of Cancer Therapy–Associated Cardiovascular Toxicity
Published: May 03, 2021
Prepared by Katherine A. Sheehan, PhD, Science and Medicine Advisor
- Cardiovascular toxicity from traditional chemotherapies has been known for some time, yet recent advances in novel targeted therapies with cardiovascular sequelae has driven the emergence of cardio-oncology as a new clinical and research field.
- Because novel cancer therapies have a broad range of potentially life-threatening complications, including heart failure, arrhythmia, myocarditis, and vascular events, the underlying molecular mechanisms are complex and include toxicology, genetic and environmental risk factors.
- This scientific statement addresses the need to understand the underlying molecular mechanisms of cardiovascular toxicity by exploring the range of preclinical cardiovascular research models that help identify biologically sound and clinically important biomarkers and cardioprotective therapies to allow for optimal use of cancer treatments while minimizing toxicities.
- The key results of the paper include the identification of preclinical models for cancer therapy-associated studies, summarizing their strengths and weaknesses, highlighting the molecular mechanisms that relate cancer and cardiovascular disease, along with opportunities to leverage this knowledge to advance cardiovascular care for all patients, with and without cancer.
- Preclinical models to study cardiovascular toxicity include cultured cell models, which are particularly suited to study cellular signaling mechanisms, drug actions and cancer therapy-associated cardiovascular toxicity in cardiomyocytes, as well as other types of cells found in the heart, including fibroblasts, pericytes, and endothelial cells.
- Organoid systems are another preclinical model that employ microphysiological systems, or ‘organs on a chip’ that incorporate human cells grown on a polymeric membrane that enable evaluation of toxicity mechanisms including crosstalk between cell types as well as the mechanisms within the cells themselves yet have limitations in their ability to fully mimic organs.
- In vivo models are evaluated which have a large range of data throughput capabilities, strengths, and weaknesses, and uses for evaluating cardiovascular toxicity of several traditional as well as novel and multimodal cancer treatments.
- Basic mechanisms of cardiovascular toxicity associated with common cancer therapies are explored, including anthracyclines, kinase inhibitors, immune therapies, and chest radiation.
- Future directions for use of these models for evaluation of the interaction of cancer therapies and cardiovascular function include exploration of shared risk factors for cancer and cardiovascular disease such as genetic or epigenetic features including the idea that cardiovascular disease is a risk factor for tumor growth, translation of the research results to clinical care, and continuing development of the field of cardio-oncology.
- The public health impact of cancer therapy-associated cardiovascular toxicity will continue to expand in importance as new cancer treatments are developed, thus continuing development and evaluation of preclinical research models will help to understand the mechanisms of molecular signaling in the heart and the impact of cancer therapies.
Citation
Asnani A, Moslehi JJ, Adhikari BB, Baik AH, Beyer AM, de Boer RA, Ghigo A, Grumbach IM, Jain S, Zhu H; on behalf of the American Heart Association Council on Basic Cardiovascular Sciences; Cardio-Oncology Science Subcommittee of Council on Genomic and Precision Medicine and Council on Clinical Cardiology; Council on Peripheral Vascular Disease; and Council on Arteriosclerosis, Thrombosis and Vascular Biology. Preclinical models of cancer therapy–associated cardiovascular toxicity: a scientific statement from the American Heart Association [published online ahead of print May 3, 2021]. Circ Res. doi: 10.1161/RES.0000000000000473