In the Heart of Cardio-Oncology: The Targets and Biomarkers of Cardiotoxicity in Anticancer Drugs

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 ha...

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Main Author: Vera Marisa Costa
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Medical Sciences Forum
Subjects:
Online Access:https://www.mdpi.com/2673-9992/14/1/126
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author Vera Marisa Costa
author_facet Vera Marisa Costa
author_sort Vera Marisa Costa
collection DOAJ
description 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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spelling doaj.art-8bf75fbf03904d169e81323638efd92e2023-11-17T12:58:36ZengMDPI AGMedical Sciences Forum2673-99922022-11-0114112610.3390/ECMC2022-13157In the Heart of Cardio-Oncology: The Targets and Biomarkers of Cardiotoxicity in Anticancer DrugsVera Marisa Costa0Associate Laboratory i4HB-Institute for Health and Bioeconomy, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalThe 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.https://www.mdpi.com/2673-9992/14/1/126cardio-oncologymitoxantronedoxorubicinadverse outcome pathways
spellingShingle Vera Marisa Costa
In the Heart of Cardio-Oncology: The Targets and Biomarkers of Cardiotoxicity in Anticancer Drugs
Medical Sciences Forum
cardio-oncology
mitoxantrone
doxorubicin
adverse outcome pathways
title In the Heart of Cardio-Oncology: The Targets and Biomarkers of Cardiotoxicity in Anticancer Drugs
title_full In the Heart of Cardio-Oncology: The Targets and Biomarkers of Cardiotoxicity in Anticancer Drugs
title_fullStr In the Heart of Cardio-Oncology: The Targets and Biomarkers of Cardiotoxicity in Anticancer Drugs
title_full_unstemmed In the Heart of Cardio-Oncology: The Targets and Biomarkers of Cardiotoxicity in Anticancer Drugs
title_short In the Heart of Cardio-Oncology: The Targets and Biomarkers of Cardiotoxicity in Anticancer Drugs
title_sort in the heart of cardio oncology the targets and biomarkers of cardiotoxicity in anticancer drugs
topic cardio-oncology
mitoxantrone
doxorubicin
adverse outcome pathways
url https://www.mdpi.com/2673-9992/14/1/126
work_keys_str_mv AT veramarisacosta intheheartofcardiooncologythetargetsandbiomarkersofcardiotoxicityinanticancerdrugs