Frontiers in Pharmacology (Jun 2024)

An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity

  • Sicong Xie,
  • Yuwei Sun,
  • Xuan Zhao,
  • Yiqun Xiao,
  • Fei Zhou,
  • Liang Lin,
  • Wei Wang,
  • Bin Lin,
  • Zun Wang,
  • Zixuan Fang,
  • Lei Wang,
  • Yang Zhang,
  • Yang Zhang

DOI
https://doi.org/10.3389/fphar.2024.1406247
Journal volume & issue
Vol. 15

Abstract

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Anthracycline drugs mainly include doxorubicin, epirubicin, pirarubicin, and aclamycin, which are widely used to treat a variety of malignant tumors, such as breast cancer, gastrointestinal tumors, lymphoma, etc. With the accumulation of anthracycline drugs in the body, they can induce serious heart damage, limiting their clinical application. The mechanism by which anthracycline drugs cause cardiotoxicity is not yet clear. This review provides an overview of the different types of cardiac damage induced by anthracycline-class drugs and delves into the molecular mechanisms behind these injuries. Cardiac damage primarily involves alterations in myocardial cell function and pathological cell death, encompassing mitochondrial dysfunction, topoisomerase inhibition, disruptions in iron ion metabolism, myofibril degradation, and oxidative stress. Mechanisms of uptake and transport in anthracycline-induced cardiotoxicity are emphasized, as well as the role and breakthroughs of iPSC in cardiotoxicity studies. Selected novel cardioprotective therapies and mechanisms are updated. Mechanisms and protective strategies associated with anthracycline cardiotoxicity in animal experiments are examined, and the definition of drug damage in humans and animal models is discussed. Understanding these molecular mechanisms is of paramount importance in mitigating anthracycline-induced cardiac toxicity and guiding the development of safer approaches in cancer treatment.

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