Mitigating Trastuzumab-Doxorubicin Cardiotoxicity With Multiscale Quantitative Systems Toxicology and PBPK-Toxicodynamic Predictive Modeling Framework.

ABSTRACT: Doxorubicin (DOX) and trastuzumab (TmAb) are widely used to treat HER2-positive breast cancer (BC), as monotherapies and in combination (DOX + TmAb). While highly effective, their combined use significantly increases the risk of irreversible cardiotoxicity, posing a major clinical concern. B-type natriuretic peptide (BNP) and NT-proBNP are serum biomarkers of early cardiotoxicity. Understanding the dynamic relationship between these biomarkers and intracellular apoptosis pathways is key to predicting and mitigating treatment-induced cardiotoxicity. This study aims to extend a previously developed multiscale modeling framework of DOX-induced cardiotoxicity to include DOX + TmAb combinatorial effects and to predict clinical outcomes. Human cardiomyocytes were exposed to different concentrati

SUBMITTER: Yu S 

PROVIDER: S-EPMC12521046 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature