Chemotherapy Induced Cognition Impairment - Mechanisms and Prevention

Most current cancer treatments involve the use of chemotherapeutic drugs, which have several known side effects. Prominent among them are neurotoxicities, which have a dramatic impact on the quality of life. Pediatric cancer survivors are disproportionately affected by quality of life issues due to their long life ahead after cancer therapy. We made an important discovery that a major cause of brain injury due to chemotherapy involves generation of reactive oxygen species (ROS) leading to defects in cognition and executive function. We recently discovered an early biomarker of this chemotherapeutic drug induced injury in the form of extracellular vesicles (EV) that carry proteins damaged by ROS. In this proposal, we will test the hypothesis that EVs are biomarkers of chemotherapy induced injury in pediatric cancer patients and that inclusion of an FDA approved ROS-mitigating drug during chemotherapy will prevent the adverse effects of chemotherapy thus improving their quality of life.