Exercise Cardio-Oncology: Exercise as a Potential Therapeutic Modality in the Management of Anthracycline-Induced Cardiotoxicity

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.

The pediatric oncology exercise field speeds up to address important issues regarding chemotherapy-related cardiotoxicity

“…A state-ofthe-art review recently highlighted the importance of exercise in childhood cancer survivors and its key role in preventing chemotherapy-related cardiotoxicity (15). Indeed, chemotherapy-related cardiotoxicity leads to cardiac dysfunctions (e.g., decline in left ventricular ejection fraction), because of mitochondrial biogenesis impairment (36), whereas exercise stimulates mitochondrial biogenesis (37). Moreover, observational studies have reported that exercise in childhood cancer survivors improves left ventricular ejection fraction (38, 39) and markers of cardiovascular health (33,40).…”

Cardio-Oncology Rehabilitation and Telehealth: Rationale for Future Integration in Supportive Care of Cancer Survivors

“…Cancer survivors have been found to have a several-fold increased incidence of cardiovascular risk factors (9), and this condition causes a higher risk of premature morbidity and mortality. To mitigate the risk, it has recently been strongly recommended to integrate a model of comprehensive cardiac rehabilitation, also called Cardio-Oncology REhabilitation (CORE), for the population of cancer patients and survivors (10)(11)(12).…”

The Impact of Exercise on Cardiotoxicity in Pediatric and Adolescent Cancer Survivors: A Scoping Review

“…Currently, CTRCD prevention methods focus on minimizing radiation exposure and cumulative anthracycline dose. Strategies also include liposomal encapsulated anthracyclines delivery [ 10 ] and improvements in radiation therapy that exhibit reduced cardiotoxic properties while maintaining high antineoplastic effects [ 11 ]. Unfortunately, these strategies do not apply to all cases [ 11 ] and do not fully mitigate CTRCD risk [ 10 ].…”

“…Strategies also include liposomal encapsulated anthracyclines delivery [ 10 ] and improvements in radiation therapy that exhibit reduced cardiotoxic properties while maintaining high antineoplastic effects [ 11 ]. Unfortunately, these strategies do not apply to all cases [ 11 ] and do not fully mitigate CTRCD risk [ 10 ]. Dexrazoxane is the only widely used pharmaceutical for preventing anthracycline-induced CTRCD [ 3 , 12 ].…”

“…Further, in adult breast cancer survivors, exercise is shown to decrease CTRCD as indicated by significant improvements in aerobic capacity [ 22 , 23 , 24 , 25 , 26 , 27 ], cardiac biomarker levels [ 28 , 29 ], strain [ 23 , 29 ], and resting heart rate [ 22 , 23 , 30 ]. Despite the plethora of evidence in preclinical animal models and adult breast cancer survivors, there is minimal research on other cancer populations, including CACS [ 10 ]. While observational studies indicate that low physical activity levels are associated with an increased incidence of cardiac dysfunction in CACS [ 31 , 32 ], few interventional exercise trials have been conducted.…”