Excessive autophagic degradation of MYLK3 causes sunitinib-induced cardiotoxicity

Researchers studied sunitinib, a receptor tyrosine kinase inhibitor used for the treatment of imatinib-resistant GIST that has caused patients to develop reduced heart function and arrhythmia. This research used the human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) model to reveal that sunitinib leads to cardiomyocyte death, disorganized heart muscle, and irregular calcium handling. A key finding is that sunitinib promotes the degradation of MYLK3, a protein essential for heart function, through an excessive autophagic process. The study suggests that targeting MYLK3, potentially through therapies like omecamtiv mecarbil, could offer a protective strategy against sunitinib's adverse cardiac effects.