Summary
Published in Science Translational Medicine (2025), this study developed a multiscale profiling platform integrating hiPSC-derived cardiomyocytes, 3D cardiac microtissues, and computational modeling to systematically assess tyrosine kinase inhibitor (TKI) cardiotoxicity. The research identified the mechanosensitive ion channel PIEZO1 as a druggable cardioprotective target, with pharmacological activation by Yoda1 rescuing TKI-induced cardiac dysfunction. 3D Petri Dish® micro-molds were used to generate uniform cardiac microtissues for high-throughput contractility and calcium imaging assays.
❤️ Cardiovascular
Multiscale profiling of tyrosine kinase inhibitor cardiotoxicity reveals mechanosensitive ion channel PIEZO1 as cardioprotective
Science Translational Medicine, 2025 · Manhas, A., et al 2025 Manhas, A., et al
Cite as: Citation: Manhas, A., et al. Multiscale profiling of tyrosine kinase inhibitor cardiotoxicity reveals mechanosensitive ion channel PIEZO1 as cardioprotective. Science Translational Medicine 2025 doi.org/10.1126/scitranslmed.adv9403
Key Discoveries
- Systematic TKI cardiotoxicity profiling — Electrophysiological, contractile, and transcriptomic analyses revealed that the cancer drugs ponatinib, sorafenib, and sunitinib disrupt calcium handling and contractile function at clinically relevant concentrations.
- PIEZO1 identified as key mediator — Multiscale profiling pinpointed the mechanosensitive ion channel PIEZO1 as a central mediator of TKI-induced cardiotoxicity, representing a novel therapeutic target.
- Yoda1 rescues cardiac function — Pharmacological activation of PIEZO1 with the small molecule Yoda1 restored calcium transient kinetics, contractile function, and electrophysiological properties in TKI-treated cardiac microtissues.
- Comprehensive preclinical framework — The platform establishes a new standard for preclinical cardiotoxicity assessment of cancer therapeutics, integrating multiple biological scales.
3D Petri Dish® Application
3D Petri Dish®