[Cardiotoxicity risk assessment of anticancer drugs by focusing on mitochondrial quality of human iPS cell-derived cardiomyocytes]

Nihon Yakurigaku Zasshi. 2025;160(1):9-12. doi: 10.1254/fpj.24056.
[Article in Japanese]

Abstract

Currently, a variety of anticancer agents are used in the treatment of cancer. Since anticancer agents are used continuously over a long time, they carry the risk of side effects. One of the major side effects is cardiac dysfunction. For example, doxorubicin, an anthracycline-type anticancer agent, is clinically restricted because of its dose-dependent cardiotoxicity. Cardiotoxicity includes decreased ejection fraction, arrhythmias, and congestive heart failure, all of which are associated with high mortality rates. Therefore, it is important to assess the risk of cardiotoxicity of anticancer agents in advance. Cardiomyocytes require energy to beat and retain an abundance of mitochondria. We established quantitative measurements of mitochondrial length and respiratory activities using cardiomyocytes. We found that exposure of human iPS cell-derived cardiomyocytes (hiPSC-CMs) to anticancer agents with reported cardiotoxicity enhanced mitochondrial hyperfission and the oxygen consumption rate was significantly reduced. Knockdown of dynamin-related protein 1 (Drp1), mitochondrial fission-accelerating GTP-binding protein, suppressed mitochondrial hyperfission in hiPSC-CMs. This indicates that visualizing mitochondrial functions in hiPSC-CMs will be helpful in assessing the risk of cardiotoxicity caused by anticancer agents and that maintaining mitochondrial quality will become a new strategy to reduce anticancer agents-induced cardiotoxicity. In this review, we present the evaluation of cardiotoxicity targeting mitochondrial quality in anticancer agents, using osimertinib, a non-small cell lung cancer drug, as an example.

Publication types

  • Review
  • English Abstract

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / pharmacology
  • Cardiotoxicity* / etiology
  • Humans
  • Induced Pluripotent Stem Cells* / drug effects
  • Mitochondria* / drug effects
  • Mitochondria* / metabolism
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism
  • Myocytes, Cardiac* / drug effects
  • Myocytes, Cardiac* / metabolism
  • Risk Assessment

Substances

  • Antineoplastic Agents