Chest radiotherapy and systemic chemotherapy are the effective treatment modalities for numerous types of cancers, including Hodgkin lymphoma and bone cancers among others. Unfortunately, cancer therapeutics have significant deleterious effects on the heart that are far more pronounced in patients receiving the therapy at younger age. One of the most serious, and poorly understood side effects is the delayed effect of cancer therapeutics on the heart muscle. Epidemiological studies indicate that the majority of patients undergoing chest radiotherapy during adolescence and young adulthood develop fibrosis in the cardiac muscle and are six times more likely to develop heart failure. Similarly,...

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Chest radiotherapy and systemic chemotherapy are the effective treatment modalities for numerous types of cancers, including Hodgkin lymphoma and bone cancers among others. Unfortunately, cancer therapeutics have significant deleterious effects on the heart that are far more pronounced in patients receiving the therapy at younger age. One of the most serious, and poorly understood side effects is the delayed effect of cancer therapeutics on the heart muscle. Epidemiological studies indicate that the majority of patients undergoing chest radiotherapy during adolescence and young adulthood develop fibrosis in the cardiac muscle and are six times more likely to develop heart failure. Similarly, anthracycline remain a leading cause of cardiovascular morbidity and mortality after cancer treatment. Unfortunately, how genotoxic cancer therapeutic agents affect heart muscle cells (known as cardiomyocytes), and whether this injury can be prevented remain unknown. Radiotherapy and chemotherapy result in damage to the DNA of cancer cells which results in slowing the rate of cancer growth, and because the heart muscle cells generally divides very slowly, the effect of cancer therapeutic agents on heart muscle renewal has generally been underappreciated. Our group was the first to describe the effect of DNA damage on heart muscle renewal. We showed that exposure to high levels of oxygen after birth stops heart muscle growth by inducing oxidative DNA damage. Our preliminary results show that radiation-induced DNA damages are irreparable in adult cardiomyocytes. Additionally, we found that this genotoxic stress triggers an increase in cardiomyocyte size, a phenomenon known as hypertrophy, which is a heart muscle pathology that results in cardiac dysfunction. Therefore, we propose to examine how chemotherapy and radiotherapy cause cardiomyocyte hypertrophy and identify the sites where these cancer therapies exert their damage within in cardiomyocytes.

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