Children's Mercy Hospitals & Clinics Archives

2019

Young Investigator

Glenson Samuel

Kansas City, MO

Executive Summary: Ewing Sarcoma (EWS) is an aggressive cancer of the bone that disproportionally afflicts children and young adults. Despite intensive therapy consisting of high-dose chemotherapy with the addition of surgery and/or radiation therapy, 70% of patients with relapsed and metastatic EWS will succumb to their disease. The continual failure to improve upon the overall survival for these patients highlights the critical need for rapid translation of novel therapeutic strategies. Advancements in personalized medicine have shown promise for providing disease and tumor-specific treatments. In EWS, a form of RNAs referred to as microRNAs (miRNAs), have been shown to be highly dysregulated and play a crucial role in controlling several genes essential to multiple biological functions in the tumor. The development of several anti-cancer therapies utilizing or targeting miRNAs with a goal of improving outcomes in various cancers are currently in process. We have recently identified a panel of miRNAs with potential therapeutic benefits in EWS. Relevant to our proposed studies, these miRNAs have been shown to be enriched in small extracellular vesicles termed ‘exosomes’. More importantly, in tumor cells, exosomes are readily secreted, taken up and can serve as a shuttle for many molecules, including miRNAs. Here, we propose to molecularly engineer exosomes to carry miRNA molecules targeting EWS tumor cells and test them in animal models, in order to develop novel therapeutics to enhance front line treatment in metastatic patients and reduce the incidence of therapy resistance and/or relapse. The proposed studies will provide the scientific infrastructure and rationale of exploring new therapeutic approaches for treating children and young adults with EWS to improve overall survival.