Funding outcome

As a result of advanced diagnosis and treatment, many children survive their cancers. Although this is very promising, some of these children develop long-term side effects of the anticancer treatment received during childhood. For instance, doxorubicin (which is a very effective anticancer medication widely used to treat several types of childhood cancers) is known to cause minor injury to the hearts of these young cancer survivors, which can cause more pronounced heart issues later in life. Despite the clinical relevance, very little is known about how doxorubicin causes this injury in the hearts of childhood cancer survivors, and what is the best way to prevent it. Importantly though, recent work in the adult heart suggests that supplementation of ketones, small molecules produced in the liver that are then released into the circulation to be used systemically, prevents tumor growth, and inhibits activation of cardiac inflammation. Interestingly, previous work from our group suggests that cardiac inflammatory signaling is a key initiator of childhood doxorubicin-induced cardiac injury. Based on this, we are studying how dietary ketone supplementation may prevent early life chemotherapy-induced injury in the heart, and how that impacts life-long cardiac function following aging.