Key result
Extending iPS cardiomyocyte exposure to 8 days better reveals cardiotoxicity differences between doxorubicin and erlotinib.
Why the study?
The cardiotoxicity mechanisms of anti-cancer drugs remain unknown, and a sensitive assay system for cardiotoxicity is needed.
Does continued exposure to anti-cancer drugs improve the predictive power for cardiotoxicity in human iPS cell-derived cardiomyocytes?
Does continued exposure to anti-cancer drugs improve the predictive power for cardiotoxicity in human iPS cell-derived cardiomyocytes?
Extended exposure (8 days) of human iPS cell-derived cardiomyocytes to anti-cancer drugs improves the predictive power of in vitro cardiotoxicity assays compared to standard 3-day exposure.
Prolonged iPS-CM exposure may improve cardiotoxicity detection sensitivity; leaves open clinical translation and validation.
Although the cardiotoxicity of anti-cancer drugs is an important issue, the underlying mechanisms remain unknown. To develop a sensitive assay system for cardiotoxicity, we examined effects of anti-cancer drugs on contractile functions of human iPS cell-derived cardiomyocytes by using non-invasive motion field imaging analysis with extended drug exposure time. We succeeded in continuously measuring stable contractile function. The continued exposure revealed that the difference in cardiotoxicity between cardiotoxic doxorubicin and less toxic erlotinib was more evident after 8 days of treatment than with 3 days of treatment, suggesting that continued exposure improved the predictive power for cardiotoxicity of anti-cancer drugs.
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Sakamoto et al. (2019) studied Cardiotoxicity of anti-cancer drugs. Continued exposure to anti-cancer drugs (doxorubicin) vs. Erlotinib / shorter exposure (3 days) was evaluated on Difference in cardiotoxicity (contractile function). Continued exposure of human iPS cell-derived cardiomyocytes to anti-cancer drugs for 8 days made the difference in cardiotoxicity between doxorubicin and erlotinib more evident than 3 days.
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