Understanding and Preventing Healthy Tissue Damage in Pediatric Cancer Patients
Background
Treatment of human cancers with chemotherapy or radiation has led to the successful eradication of malignancies in millions of patients, yet the cell death induced in healthy tissues drastically limits the use of these crucial therapies. This is especially true in pediatric patients who experience more damaging side effects from treatment. For example, children with many types of cancers are commonly treated with doxorubicin, which is an extremely effective anti-cancer agent and cures many patients. However, children experience higher levels of heart toxicity from doxorubicin treatment than adults for reasons that are unknown. In addition, brain irradiation is a very effective treatment for many childhood brain tumors, yet it also causes cell death in healthy brain cells, frequently resulting in a devastating loss of intelligence which severely reduces quality of life. Adults treated with brain irradiation exhibit dramatically less toxicity than children but the basis for this difference in sensitivity is unknown. Using BH3 profiling, an innovative tool to measure how close cells are to the threshold of cell death, we recently observed novel and striking differences in the how apoptosis is regulated in vital tissues including the brain and heart.
Project Goals
Within this project, we plan to first develop a comprehensive understanding of how differential regulation of cell death affects cell fate in response to damage or stress in children. We will then identify the how the body controls these pathways. These studies may be leveraged to develop treatment strategies and agents that will reduce toxicity and improve patient's lives.
