【Introduction】Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with various types of cancer. Growing evidence suggest that cancer therapy-related cardiotoxicity has become important as the serious adverse event associated with many TKIs. Epidermal growth factor receptor-TKI (EGFR-TKI), which has demonstrated efficacy in patients with non-small-cell lung cancer, has been reported to have a risk of cardiac dysfunction. However, cardiotoxicity of EGFR-TKIs has not been fully understood. Here we evaluated the effects of EGFR-TKIs on contractility using human iPS cell-derived cardiomyocytes (hiPSC-CMs).
【Methods】We used iCell cardiomyocyte 2.0 (FCDI). Motion analyses were performed using a cell motion imaging system (SI8000, Sony). Real-world pharmacovigilance data were analyzed by a reporting odds ratio from FDA Adverse Event Reporting System (FAERS).
【Results】We found that several EGFR-TKI decreased contraction velocity in a concentration-dependent manner, while other EGFR-TKIs did not. To confirm the in vitro data, we analyzed the cardiotoxicity risk of EGFR-TKIs by the real-world pharmacovigilance data from FAERS. EGFR-TKI, which decreased contraction velocity in hiPSC-CMs, was significantly associated with cardiac failure and decreased ejection fraction.
【Conclusion】Thus, contractile analysis of hiPSC-CMs would be useful to assess TKI-induced cardiac dysfunction in human. We are planning to evaluate other types of TKIs with hiPSC-CMs.