期刊
CLINICAL SCIENCE
卷 135, 期 10, 页码 1311-1332出版社
PORTLAND PRESS LTD
DOI: 10.1042/CS20200301
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资金
- Padres Pedal the Cause/RADY [PTC2020]
- UC San Diego Moore Cancer Center, Specialized Cancer Control Support Grant [NIH/NCI P30CA023100]
- VMRF Pilot Project Award
- UC San Diego ANES Research Seed Award
- Merck Investigator Studies Program and Scientific Engagements
Anthracyclines are effective chemotherapeutic agents commonly used in cancer treatment, but their use can lead to cardiovascular toxicity such as cardiomyopathy and heart failure.
Anthracyclines are highly effective chemotherapeutic agents that remain a cornerstone of contemporary therapeutic regimens for a number of malignancies despite a remarkable number of recent advances in cancer therapeutics. Anthracyclines are used in up to 50-70% of adult lymphoma patients [1] and over half of childhood cancer patients [2], and remain the first-line therapeutic agent for soft tissue sarcomas [3]. Despite the increased and preferential use of taxane-based regimens, a significant proportion of breast Anthracyclines are effective chemotherapeutic agents, commonly used in the treatment of a variety of hematologic malignancies and solid tumors. However, their use is associated with a significant risk of cardiovascular toxicities and may result in cardiomyopathy and heart failure. Cardiomyocyte toxicity occurs via multiple molecular mechanisms, including topoisomerase II-mediated DNA double-strand breaks and reactive oxygen species (ROS) formation via effects on the mitochondrial electron transport chain, NADPH oxidases (NOXs), and nitric oxide synthases (NOSs). Excess ROS may cause mitochondrial dysfunction, endoplasmic reticulum stress, calcium release, and DNA damage, which may result in cardiomyocyte dysfunction or cell death. These pathophysiologic mechanisms cause tissue-level manifestations, including characteristic histopathologic changes (myocyte vacuolization, myofibrillar loss, and cell death), atrophy and fibrosis, and organ-level manifestations including cardiac contractile dysfunction and vascular dysfunction. In addition, these mechanisms are relevant to current and emerging strategies to diagnose, prevent, and treat anthracycline-induced cardiomyopathy. This review details the established and emerging data regarding the molecular mechanisms of anthracycline-induced cardiovascular toxicity.
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