Chronotherapy as a novel strategy to limit anthracycline-induced cardiotoxicity
Anthracycline cardiotoxicity is a severe chemotherapeutic side effect that can lead to heart failure in cancer patients and survivors. Chronomodulated chemotherapy is a promising preventive strategy that encompasses the adjustment of anthracycline administration time to the circadian rhythms (24-hour rhythms) of the body. Circadian rhythms play a major role in cardiovascular physiology and disease and may lead to a time-dependent variation in cardiac sensitivity to anthracyclines. In this review, all available evidence on the topic of chronomodulated anthracyclines for cardiotoxicity reduction and/or oncological efficacy enhancement is summarized. In total, 3 in vitro studies, 12 animal studies, and 9 clinical studies were included. Potential mechanistic explanations involved 24-hour variation in oxidative stress regulation, DNA damage repair, and systemic or intracellular pharmacokinetics. We identified a hypothesized optimal time frame from 3 to 11 AM for anthracycline administration in humans, based on extrapolation of findings in animal studies.
Authors
- Joost P. G. Sluijter (ORCID: https://orcid.org/0000-0003-2088-9102)
- Alwin D. R. Huitema (ORCID: https://orcid.org/0000-0003-1939-4639)
- Yvonne Koop (ORCID: https://orcid.org/0000-0001-6150-0859)
- Pieterjan Dierickx (ORCID: https://orcid.org/0000-0002-1709-1477)
- Linda W. van Laake (ORCID: https://orcid.org/0000-0002-5027-0661)
- Pasquale F. Innominato (ORCID: https://orcid.org/0000-0002-0653-8261)
- Markella I Printezi (ORCID: https://orcid.org/0000-0001-6265-6230)
- Anne M. May (ORCID: https://orcid.org/0000-0001-7551-9200)
- Annabelle Ballesta (ORCID: https://orcid.org/0000-0001-7204-1205)
- Ilse R. Kelters (ORCID: https://orcid.org/0009-0002-5001-4665)
- Françis Lévi (ORCID: https://orcid.org/0000-0003-1364-7463)
- Pieter A. Doevendans (ORCID: https://orcid.org/0000-0002-6257-7169)
- Jacqueline Van Dam
- Arco J. Teske (ORCID: https://orcid.org/0000-0001-5305-1619)
Institutions
- Betsi Cadwaladr University Health Board (GB)
- Inserm (FR)
- Utrecht University (NL)
- Heidelberg University (DE)
- Université Paris-Saclay (FR)
- University Hospital Heidelberg (DE)
- Karolinska Institutet (SE)
- University Medical Center Utrecht (NL)
- University of Warwick (GB)
- Max Planck Institute for Heart and Lung Research (DE)
- Netherlands Heart Institute (NL)
- Laboratoire d'études sur les monothéismes (FR)
- German Centre for Cardiovascular Research (DE)
- Cardio-Pulmonary Institute (DE)
- Institut Curie (FR)
Publication Details
- Journal
- Cardiovascular Research
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1093/cvr/cvaf179
- Citations
- 1
- Primary Topic
- Chemotherapy-induced cardiotoxicity and mitigation
- Type
- article
- Field-Weighted Citation Impact
- 1.39
Funders
- Institut National de la Santé et de la Recherche Médicale
- ZonMw
- Universiteit Utrecht
- Hartstichting
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Horizon 2020 Framework Programme