Excessive autophagic degradation of MYLK3 causes sunitinib-induced cardiotoxicity.

ABSTRACT: Sunitinib is a receptor tyrosine kinase inhibitor used for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors. Clinical data have shown that patients receiving sunitinib develop reduced cardiac function, arrhythmia and heart failure, thereby largely limiting its clinical use. However, the molecular mechanisms underlying sunitinib-induced arrhythmogenesis remain unclear. Here, utilizing the human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model, we found that sunitinib caused a variety of deleterious phenotypes, including cardiomyocyte death, sarcomeric disorganization, irregular Ca²⁺ transients, impaired ATP2A2a/SERCA2a (ATPase sarcoplasmic/endoplasmic reticulum Ca²⁺ transporting 2a) activity, arrhythmia, an

SUBMITTER: Pan Z 

PROVIDER: S-EPMC12758171 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature