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Mol Pharmacol. 2019 Aug;96(2):219-232. doi: 10.1124/mol.119.115725. Epub 2019 Jun 4.

Insights into Doxorubicin-induced Cardiotoxicity: Molecular Mechanisms, Preventive Strategies, and Early Monitoring.

Author information

1
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida.
2
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida sihem.bihorel@cop.ufl.edu.

Abstract

Doxorubicin (DOX) is one of the most effective anticancer drugs to treat various forms of cancers; however, its therapeutic utility is severely limited by its associated cardiotoxicity. Despite the enormous amount of research conducted in this area, the exact molecular mechanisms underlying DOX toxic effects on the heart are still an area that warrants further investigations. In this study, we reviewed literature to gather the best-known molecular pathways related to DOX-induced cardiotoxicity (DIC). They include mechanisms dependent on mitochondrial dysfunction such as DOX influence on the mitochondrial electron transport chain, redox cycling, oxidative stress, calcium dysregulation, and apoptosis pathways. Furthermore, we discuss the existing strategies to prevent and/or alleviate DIC along with various techniques available for therapeutic drug monitoring (TDM) in cancer patients treated with DOX. Finally, we propose a stepwise flowchart for TDM of DOX and present our perspective at curtailing this deleterious side effect of DOX.

PMID:
31164387
DOI:
10.1124/mol.119.115725

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