Abstract
Anthracyclines are one of the most effective chemotherapy agents and have revolutionized cancer therapy. However, anthracyclines can induce cardiac injuries through ‘multiple-hits', a series of cardiovascular insults coupled with lifestyle risk factors, which increase the risk of developing short- and long-term cardiac dysfunction and cardiovascular disease that potentially lead to premature mortality following cancer remission. Therefore, the management of anthracycline-induced cardiotoxicity is a serious unmet clinical need. Exercise therapy, as a non-pharmacological intervention, stimulates numerous biochemical and physiologic adaptations, including cardioprotective effects, through the cardiovascular system and cardiac muscles, where exercise has been proposed to be an effective clinical approach that can protect or reverse the cardiotoxicity from anthracyclines. Many preclinical and clinical trials demonstrate the potential impacts of exercise on cardiotoxicity; however, the underlying mechanisms as well as how to implement exercise in clinical settings to improve or protect against long-term cardiovascular disease outcomes are not clearly defined. In this review, we summarize the current evidence in the field of “exercise cardio-oncology” and emphasize the utilization of exercise to prevent and manage anthracycline-induced cardiotoxicities across high-risk and vulnerable populations diagnosed with cancer.
Highlights
Developed in the 1960s, anthracyclines are one of the most effective chemotherapies, including doxorubicin, daunorubicin, epirubicin, and idarubicin [1, 2]
In this review, we summarize the mechanisms of anthracyclineinduced cardiotoxicities and present the current pre-clinical and clinical exercise cardio-oncology literature to describe and emphasize the utilization of exercise to prevent, improve, and manage anthracycline-induced cardiotoxicities in individuals diagnosed with cancer
This study primarily assessed acute and chronic chemotherapy-induced cardiotoxicities monitored by cardiorespiratory fitness, cardiac troponin T, a biomarker used in detecting acute cardiac damage, and NT-pro-BNP, a protein secreted by cardiomyocytes in response to cardiac wall stress a marker of long-term cardiac remodeling [91]
Summary
Developed in the 1960s, anthracyclines are one of the most effective chemotherapies, including doxorubicin, daunorubicin, epirubicin, and idarubicin [1, 2]. Many strategies have been utilized by clinicians to reduce the risk of anthracycline-induced cardiotoxicities These include: (a) the restriction of the cumulative dose of anthracyclines, to those with cardiovascular disease (CVD) risk factors, (b) use of pegylated liposomes to deliver the therapy, (c) concurrent prescription of dexrazoxane, the only Food and Drug Association approved drug to prevent cardiotoxicities in survivors receiving anthracyclines [9, 13], and (d) long-term monitoring throughout cancer remission for changes in cardiac function and health. “Exercise cardio-oncology,” a term to our knowledge that is inaugurally coined here, is defined as the application of exercise as a non-pharmacological strategy to prevent, manage, and improve cancer- and treatment-induced cardiotoxicities This is an underdeveloped field with few longitudinal clinical trials examining the effect of long-term interventions as potentially beneficial strategies for cardioprotection in anthracycline-treated cancer survivors.
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