Targeting apoptosis to prevent cancer therapy-induced cardiovascular dysfunction in pediatric patients

Dr. Kristopher Sarosiek, Ph.D. – President and Fellows of Harvard College, Harvard T. H. Chan School of Public Health, Boston, MA

Cancers commonly arising in children including leukemias, lymphomas and solid tumors of the nervous system are a leading cause of death and long-term disability. These cancers are typically treated with radiation and chemotherapies, which can control or even eradicate tumors in pediatric patients. However, these treatments can also severely damage cells within the developing heart and vascular system, causing life-long cardiovascular dysfunction including chronic heart failure and stroke. We recently discovered that cell death is regulated differently in our varying healthy tissues during development and early childhood. In fact, cells within the developing heart and vasculature are highly prone to dying via apoptosis, which may explain why many childhood cancer survivors experience cardiovascular disease. However, it is unclear which cells within the developing heart and vasculature are particularly at risk of dying in response to cancer therapies and how the loss of each cell type contributes to long-term dysfunction. Our proposal will build our understanding of how the regulation of apoptosis in young heart and vasculature affects both short-term therapy induced toxicity as well as long-term dysfunction. In addition, our studies will test the extent to which blocking cell death in healthy tissue will prevent therapy-induced dysfunction to enable the development of treatments that will reduce cardiovascular toxicity and improve the lives of pediatric cancer patients.