Effects of tyrosine kinase inhibitors on rat isolated heart function and protein biomarkers indicative of toxicity

The ex-vivo assay is a sensitive and predictive model for assessing changes in heart function and biomarkers of toxicity and injury. This assay demonstrates the potential for sunitinib and sorafenib to cause cardiac toxicity in humans. Also, TNFα appears to be a biomarker in the heart prior to injury. Due to its versatility, the isolated heart assay has potential to fill gaps in cardiac safety testing early in drug development.