Methods for predicting cardiac toxicity

Abstract

Methods are disclosed for determining whether organ toxicity, particularly cardiotoxicity, will occur in a patient selected for treatment with various kinase inhibitors, such as tyrosine kinase inhibitors, more particularly erbB inhibitors such as Herceptin. In addition, methods are disclosed for determining whether a potential drug is likely to produce a cardiotoxic effect. The methods involve analyzing lipid levels or the expression fatty acid oxidation enzymes, pAMP activated protein kinase, glucose uptake, to determine whether a fatty acid oxidation disorder is present. The identification of a fatty acid oxidation disorder can be used as a predictor of toxicity, especially cardiac toxicity, and as an indication that organ function should be carefully monitored if a drug such as a tyrosine kinase inhibitor is administered. Methods are also disclosed for protecting organs from metabolic stress and for the treatment of cells, such as adipocytes, to reduce their lipid content.

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