This new process of treating fusion-driven pediatric sarcomas centers around the nuclear receptor NR0B1, which has the ability to impede and suppress the response of other nuclear receptors to their natural ligands. Currently there are no targeted therapies approved for fusion-driven pediatric sarcomas, establishing what is likely the first demonstration that disrupting NR0B1 can unmask nuclear receptor–dependent therapeutic responses in a pediatric cancer, offering a novel and potentially safer treatment approach for fusion‑driven sarcomas.