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Baichun Yang and Thomas Papoian Tyrosine kinase inhibitor (TKI)-induced cardiotoxicity: approaches to narrow the gaps between preclinical safety evaluation and clinical outcome Journal of Applied Toxicology 32

Version of Record online: 10 SEP 2012 | DOI: 10.1002/jat.2813

Tyrosine kinase inhibitors (TKI)-induced cardiac toxicity in cancer patients was not well predicted by preclinical studies, owing to the lack of a comprehensive TKI mechanism of action and appropriate cardiac functional evaluation. To help close the gaps, additional preclinical testing is proposed, including: precise determination of the mechanism of action, cardiomyocyte cultures for screening potentially cardiotoxic drugs, functional assessments using isolated perfused heart methodology or echocardiography, and assessment of both safety and efficacy in animal models of disease.

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