Abstract A021: A human-induced pluripotent stem cell (hiPSC)-derived cardiac spheroids (hiPSC-CSs) platform for individualized cancer drug cardiotoxicity assessment.

Abstract Safety pharmacology studies are required for new drug applications in order to protect clinical trials participants and patients from potential adverse effects of pharmaceuticals. Despite this, the drug approval rate after clinical trials was less than 12% based on the US FDA data. Of those, cardiotoxicity accounted for approximately one third of the cause for drug withdrawn. The above fates have highlighted the limited prediction function of the current safety pharmacology testing methods and the need of developing alternative methods which are more effective. Additionally, cardiotoxicity from drug treatment of cancer patients is also common and could lead to heart failure following therapy. The fate that individual patients have different cardiotoxicity response to the same cancer drug highlights the need of developing new methods for individualized cancer drug cardiotoxicity assessment. Human pluripotent stem cell (hiPSC) - derived cardiac spheroid is a three-dimensional in vitro model of the human heart, which contains diverse cardiac-like cell types and shows rhythmic contractions, thus it has emerged as a promising 3D in vitro model of the human heart. We developed a microfluidic chip-based platform to generate hiPSC-derived cardiac spheroids for cardiotoxicity testing. The microfluidic chip can form large numbers uniform hiPSCs aggregates which can subsequently be differentiated into contracting cardiac spheroids in well-controlled conditions. The chip is operated with manual pipetting and allows the cells to be observed by using conventional microscopes, making it easy to use in a regular laboratory. Medium exchange is also straightforward to perform through the microchannel of the chip during the long-term differentiation culture and drug testing of the hiPSC-CSs. The potential of our platform for individualized cardiotoxicity evaluation is demonstrated by testing cardiotoxicity of doxorubicin on hiPSC-derived cardiac spheroids. Citation Format: Chia-Hsien Hsu. A human-induced pluripotent stem cell (hiPSC) -derived cardiac spheroids (hiPSC-CSs) platform for individualized cancer drug cardiotoxicity assessment. abstract. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31 (23Suppl): Abstract nr A021.