期刊
CURRENT TREATMENT OPTIONS IN ONCOLOGY
卷 22, 期 2, 页码 -出版社
SPRINGER
DOI: 10.1007/s11864-020-00812-1
关键词
Cardiotoxicity; Cardiac metabolism; Doxorubicin
类别
资金
- Universita degli Studi di Torino within the CRUI-CARE Agreement
Heart failure is increasingly being recognized as a major complication of chemotherapy regimens, with doxorubicin (DOXO) remaining a commonly used but cardiotoxic anticancer agent. The molecular level effects of DOXO on the heart include mitochondrial dysfunction, DNA damage, and apoptosis. Dexrazoxane is currently the only FDA-approved cardioprotectant for patients treated with DOXO. However, research on the impact of DOXO on cardiac metabolism and potential pharmacological targets for prevention or treatment of DOXO cardiomyopathy is still ongoing.
Opinion statement Heart failure (HF) is increasingly recognized as the major complication of chemotherapy regimens. Despite the development of modern targeted therapies such as monoclonal antibodies, doxorubicin (DOXO), one of the most cardiotoxic anticancer agents, still remains the treatment of choice for several solid and hematological tumors. The insurgence of cardiotoxicity represents the major limitation to the clinical use of this potent anticancer drug. At the molecular level, cardiac side effects of DOXO have been associated to mitochondrial dysfunction, DNA damage, impairment of iron metabolism, apoptosis, and autophagy dysregulation. On these bases, the antioxidant and iron chelator molecule, dexrazoxane, currently represents the unique FDA-approved cardioprotectant for patients treated with anthracyclines. A less explored area of research concerns the impact of DOXO on cardiac metabolism. Recent metabolomic studies highlight the possibility that cardiac metabolic alterations may critically contribute to the development of DOXO cardiotoxicity. Among these, the impairment of oxidative phosphorylation and the persistent activation of glycolysis, which are commonly observed in response to DOXO treatment, may undermine the ability of cardiomyocytes to meet the energy demand, eventually leading to energetic failure. Moreover, increasing evidence links DOXO cardiotoxicity to imbalanced insulin signaling and to cardiac insulin resistance. Although anti-diabetic drugs, such as empagliflozin and metformin, have shown interesting cardioprotective effects in vitro and in vivo in different models of heart failure, their mechanism of action is unclear, and their use for the treatment of DOXO cardiotoxicity is still unexplored. This review article aims at summarizing current evidence of the metabolic derangements induced by DOXO and at providing speculations on how key players of cardiac metabolism could be pharmacologically targeted to prevent or cure DOXO cardiomyopathy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据