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Dr. Graves and colleagues will improve treatment for osteosarcoma, an aggressive bone cancer that frequently becomes resistant to chemotherapy. Cells that become resistant to chemotherapy often undergo adaptations to help them survive and recover. Dr. Graves will investigate how chemotherapy remodels iron usage and mitochondrial function to support survival in osteosarcoma cells. Early data suggest these cells become more dependent on energy production in the mitochondrial to survive. By impacting energy production, Dr. Graves and colleagues will test whether cancer cells become less resistant, grow more slowly, and will be less likely to spread. Dr. Graves will evaluate a new "multi-strike" treatment that delivers chemotherapy first, followed by carefully timed drugs that disrupt cancer cell metabolism before tumors can rebound. By identifying weaknesses in cells that survive chemotherapy and optimizing treatment timing, Dr. Graves and team will prevent tumor regrowth and improve outcomes in osteosarcoma.