biostudies-literatureUnknown113(10)Sasaki RJuntendo UniversityTrastuzumab-induced cardiotoxicity interferes with continued treatment in approximately 10% of patients with ErbB2-positive breast cancer, but its mechanism has not been fully elucidated. In this study, we recruited trastuzumab-treated patients with ≥30% reduction in left ventricular ejection fraction (SP) and noncardiotoxic patients (NP). From each of these patients, we established three cases of induced pluripotent stem cell-derived cardiomyocytes (pt-iPSC-CMs). Reduced contraction and relaxation velocities following trastuzumab treatment were more evident in SP pt-iPSC-CMs than NP pt-iPSC-CMs, indicating the cardiotoxicity phenotype could be replicated. Differences in ATP production, reactive oxygen species, and autophagy activity were observed between the two groups. Analysis of transcCancer science3449-3462https://www.ebi.ac.uk/biostudies/studies/S-EPMC9530879biostudies-literatureInvolvement of kallikrein-PAR2-proinflammatory pathway in severe trastuzumab-induced cardiotoxicity.PMC9530879Kashiyama TEguchi HShiga TMiyazaki SSasaki RKurebayashi NAkamatsu WSaito MHorimoto YfalseInvolvement of kallikrein-PAR2-proinflammatory pathway in severe trastuzumab-induced cardiotoxicity.Trastuzumab-induced cardiotoxicity interferes with continued treatment in approximately 10% of patients with ErbB2-positive breast cancer, but its mechanism has not been fully elucidated. In this study, we recruited trastuzumab-treated patients with ≥30% reduction in left ventricular ejection fraction (SP) and noncardiotoxic patients (NP). From each of these patients, we established three cases of induced pluripotent stem cell-derived cardiomyocytes (pt-iPSC-CMs). Reduced contraction and relaxation velocities following trastuzumab treatment were more evident in SP pt-iPSC-CMs than NP pt-iPSC-CMs, indicating the cardiotoxicity phenotype could be replicated. Differences in ATP production, reactive oxygen species, and autophagy activity were observed between the two groups. Analysis of transc2022-01-01T00:00:00Z2022 Oct2025-04-21T16:50:09.373Z2025-04-05T11:38:13.366ZS-EPMC95308793587924810.1111/cas.15508