Many novel oncology therapeutics may induce cardiotoxicity by inhibiting survival pathways which are shared by both tumors and cardiac cells. Traditional methods to assess cardiotoxicity have relied upon in vitro overexpressing human cell lines or use in vivo animal models. These models often lack the complexity of human cardiomyocytes, whereas animal models may lack predictivity due to inherent species differences. Therefore, there is a need for more predictive and specific assays that allow for multiparametric assessment of potential cardiotoxic side effects of new drugs in humans.
Using proprietary human iPSC-derived ventricular cardiomyocytes , we developed a multiparametric assay to measure potential cardiotoxic drug effects in vitro. Here, both acute and long-term effects of anticancer drugs (nilotinib, lapatinib, doxorubicin, and ponatinib) on impedance, electrophysiology (MEA), and cardiac Troponin I (cTnI) release are determined simultaneously from each well of a 48-well E-plate.
The results in this scientific poster suggest that a multiplexed analysis is crucial to investigate short- and long-term cardiac liabilities as it provides a more comprehensive readout that generates mechanism-specific cardiotoxicity profiles, leading to better prediction of drug-induced cardiotoxicity.