| Summary: | The cardiotoxicity of anticancer drugs is the second leading cause of death in cancer patients. Among other adverse effects, left ventricular ejection fraction decreases or heart failure emerges after anticancer treatments comprising old or new targeted therapies. In the last few years, our group has been trying to unveil the cardiac adverse outcome pathways of classic chemotherapeutic agents, mainly focusing on two topoisomerase inhibitors, mitoxantrone and doxorubicin. Mitoxantrone and doxorubicin both cause cumulative dose cardiotoxicity and were tested in vitro and in pre-clinical models. Results obtained in mice and rats following a clinically relevant dosing scheme were mimicked in vitro, demonstrating that the drugs change cellular redox homeostasis and promote inflammation, although in different biomarkers. Moreover, autophagy and energetic pathways were affected; the first mainly after mitoxantrone and the latter when doxorubicin was used. Thus, these drugs have distinct cardiac fingerprints. In conclusion, although their clinical cardiac effects are similar in humans, mitoxantrone and doxorubicin have different initiating cardiotoxic events. These were revealed taking into account the use of proper experimental models, clinically relevant concentrations, and Omics methods. These data are the essence in terms of promoting drug-specific cardioprotective measures in the future, for patients treated with these drugs.
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