Dr. Lemberg will study a class of sarcomas, called RAS-active sarcomas, to understand how RAS mutations tell the cancer cell to build more types of molecules called pyrimidines. Pyrimidines are very important in how cancer cells divide, generate a supportive environment, and signal within the cell. Previous studies have suggested that in RAS-active adult tumors cancer cell growth can be inhibited by using drugs called pyrimidine inhibitors. This study will systematically test the interactions between RAS signaling and pyrimidine synthesis in two types of pediatric sarcomas: rhabdomyosarcoma and malignant peripheral nerve sheath tumor. Dr. Lemberg will investigate whether pyrimidine synthesis inhibitors are effective in preventing tumor growth models of this cancer type. The overall goal is to understand whether childhood sarcomas with RAS mutations can also be treated with pyrimidine inhibitors with the eventual goal of translating these findings to the clinic.