Identification of Rhabdomyosarcoma Therapies Using an Efficient Mouse and Drosophila Repurposing Screen

Background

The most common pediatric soft tissue sarcoma, representing 3-5% of all childhood cancers, is Rhabdomyosarcoma (RMS). The most aggressive form, Alveolar RMS (ARMS), is associated with metastasis. Approximately 14% of children with RMS have metastatic disease at the time of initial diagnosis. The outcome for patients with metastatic or recurrent disease remains dismal with standard treatment: an estimated five year survival of <30%.  Together, these data emphasize a critical need to identify novel treatments that limit RMS metastasis and improve survival rates, the key goal of this proposal.

Project Goal

However, RMS is considered a relatively rare cancer, and so lacks major investment in treatment development. This type of disease may benefit from drug repurposing screens of FDA-approved compounds. Drugs identified in these screens can be prioritized quickly for clinical trials, removing years from the bench-to-bed timeframe. Based on our identification of ten drugs in our pilot screen, we hypothesize that a repurposing screen for ARMS can yield novel treatment regimens for this deadly pediatric disease. We have developed a cost-efficient, relatively high-throughput protocol for drug screens in a Drosophila ARMS model. Drugs recovered in this screen will be tested for efficacy against human ARMS cell lines and in mouse xenograft models. The FDA-approved drugs that target ARMS in these different models will be fast tracked to clinical trials.