Development of an In Vitro Test for the Optimization of Drug Diffusion in Pediatric Solid Tumors

There is significant long-term morbidity and mortality associated with the treatment of childhood cancer, and the risk of these effects continues to increase years after completion of therapy. Among childhood cancer survivors the cumulative incidence of a chronic health condition is 99% within 50 years of the original cancer diagnosis. There is a high risk for severe, disabling, or life-threatening chronic condition caused by the chemotherapy used to treat the initial malignancy. Current standards for determining chemotherapy dosage to treat solid tumor malignancies of pediatric patients is based on several factors, including the patients surface area, age, weight, and height. To reduce the long-term effects of chemotherapy in pediatric patients our group is focused on developing novel local drug delivery systems to treat solid tumors and minimize systemic effects. The aim of the current study is to develop an in vitro method to quantify drug diffusion through tumor tissue that will allow us to optimize the dose required to treat solid tumor malignancies in vivo. We hope by modeling the significant parameters that influence drug penetration of chemotherapy drugs, we can facilitate the development of innovative drug delivery methods and more effective administration of anticancer agents to better treat pediatric malignancies and improve both short-term and long-term outcomes for childhood cancer.