Energy Balance Strategies for Decreasing Chemotherapy-Induced Cardiotoxicity
Advances in chemotherapy strategies have improved survival rates for childhood cancer to 80%. However, there are >400,000 survivors where cardiac disease related to cancer therapy is the leading cause of mortality. There is a correlation between total dose of doxorubicin (Dox) and overall survival in children with sarcomas but also a direct link between Dox dose and subsequent cardiac morbidity. We demonstrated that exercise during Dox decreased acute cardiac damage without interfering with Dox efficacy.
We hypothesize that specific exercise regimens, initiated during or after Dox treatment, will decrease acute Dox-induced cardiac damage and promote rapid recovery, thereby reducing late cardiac effects and improving cardiac health in survivors. Prior to initiating a clinical trial, bio-markers must be defined to confirm the success of the intervention in each patient. Using our pediatric cardiotoxicity murine model, we will identify serum bio-markers of Dox-induced cardiotoxicity and determine whether exercise modifies these markers. Obtaining this serum profile in murine models will allow us to monitor the success of the intervention in each patient and modify accordingly. We will also determine if exercise initiated after Dox reverses late cardiotoxicity and whether exercise during or after Dox therapy improves recovery from a stress-related cardiac event such as a myocardial infarction. Exercise interventions are modifiable and can be leveraged to improve treatment outcomes and survivorship. Cardiomyopathies occur in 57% of childhood cancer survivors. Therefore, interventions that reduce Dox-induced cardiac damage can have a profound impact on cardiac morbidity in childhood cancer survivors, improving quality of life and longevity.