Epigenetic Mechanisms Involved in the Cardiovascular Toxicity of Anticancer Drugs

Frontiers in Cardiovascular Medicine

Agapios Sachinidis¹  Luying Peng²  Panagiota Papazoglou³ 

[1] Faculty of Medicine, Institute of Neurophysiology, University of Cologne, Cologne, Germany;Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;Heart Health Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China;Institute of Medical Genetics, Tongji University, Shanghai, China;School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece;

关键词: induced pluripotent stem cells;    hiPSCs;    cardiotoxicity;    heart failure;    genomics biomarkers;    anthracyclines;    anticancer therapy;    epigenetic mechanisms;   

DOI  :  10.3389/fcvm.2021.658900

来源: Frontiers

【 摘 要 】

The cardiovascular toxicity of anticancer drugs promotes the development of cardiovascular diseases. Therefore, cardiovascular toxicity is an important safety issue that must be considered when developing medications and therapeutic applications to treat cancer. Among anticancer drugs, members of the anthracycline family, such as doxorubicin, daunorubicin and mitoxantrone, are known to cause cardiotoxicity and even heart failure. Using human-induced pluripotent stem cell-derived cardiomyocytes in combination with “Omic” technologies, we identified several cardiotoxicity mechanisms and signal transduction pathways. Moreover, these drugs acted as cardiovascular toxicants through a syndrome of mechanisms, including epigenetic ones. Herein, we discuss the main cardiovascular toxicity mechanisms, with an emphasis on those associated with reactive oxygen species and mitochondria that contribute to cardiotoxic epigenetic modifications. We also discuss how to mitigate the cardiotoxic effects of anticancer drugs using available pharmaceutical “weapons.”

【 授权许可】

CC BY