Doxorubicin is a highly effective anticancer agent but causes cardiotoxicity in many patients. This study aims to identify biomarkers to predict potential cardiotoxicity before the onset of cardiac tissue damage and dysfunction in individual cancer patients. First, we established a human cellular system to model the cardiac toxicity of oncology drugs using human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs). We tested a panel of clinically used drugs including anthracyclines (doxorubicin, daunorubicin, epirubicin and idarubicin), 5-FU, Taxol, Trastuzumab, and tyrosine kinase inhibitors (sunitinb, imatinib, and sorafinib). These drugs displayed varying degrees of cytotoxicity in iPS-CMs which are generally consistent with their known cardiotoxicity patterns. Second, we found that doxorubicin selectively upregulated the expression of death receptors in iPS-CMs. As a result, the treated iPS-CMs underwent spontaneous apoptosis that was further enhanced in the presence of specific cytokines. Based on these findings, we hypothesize that the baseline levels of the predefined cytokines in blood could be predictive of cardiotoxicity associated with doxorubicin treatment in individual patients. We are currently investigating the relationships between the levels of the predefined cytokine signature in blood and cardiac events in patients who received doxorubicin or related anthracycline therapy.
Citation Format: Liqun Zhao, Baolin Zhang. Identifying biomarkers to predict cardiotoxicity of doxorubicin in individual patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2784. doi:10.1158/1538-7445.AM2017-2784