Combined BET and mTORC inhibition in fusion positive rhabdomyosarcoma
Mentor Name: Amit Sabnis
RMC-6272 and BET inhibitors can slow down tumor growth in mouse models and decrease--but not eliminate--PAX3-FOXO1 levels. If combining these drugs will completely deprive cancer cells of PAX3-FOXO1, it could potentially eradicate rhabdomyosarcoma. In this project, we will treat rhabdomyosarcoma cells with BET inhibitors, RMC-6272, and/or older, less effective mTOR inhibitors. We plan to investigate the efficacy of each drug alone and in combination to see how well they block the production of PAX3-FOXO1 RNA and protein to test our hypothesis that anti-cancer activity is directly related to how well PAX3-FOXO1 levels are suppressed. Finally, we will measure levels of PAX3-FOXO1 in banked samples of patient-derived tumors grown in mice that received combination BET/mTOR inhibitors in a separate project to confirm that this combination can effectively pull the plug on PAX3-FOXO1.
