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Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity

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Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
2
Medical Scientist Training Program, Medical College of Wisconsin; Milwaukee, WI 53226, USA
3
Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
4
Division of Radiation Health, Department of Pharmaceutical Sciences, The University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
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Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 415; https://doi.org/10.3390/cancers12020415
Received: 20 January 2020 / Revised: 8 February 2020 / Accepted: 8 February 2020 / Published: 11 February 2020
(This article belongs to the Special Issue Animal Models for Radiotherapy Research)
Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance. View Full-Text
Keywords: radiation biology; thoracic radiation therapy; normal tissue toxicity; cardiopulmonary toxicity; small animal irradiators; image-guided radiotherapy; cardiotoxicity; radiation-induced heart disease radiation biology; thoracic radiation therapy; normal tissue toxicity; cardiopulmonary toxicity; small animal irradiators; image-guided radiotherapy; cardiotoxicity; radiation-induced heart disease
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Schlaak, R.A.; SenthilKumar, G.; Boerma, M.; Bergom, C. Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity. Cancers 2020, 12, 415.

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