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Vincristine is a common and effective chemotherapy for children with leukemia, sarcomas, and brain tumors. Unfortunately, many children who receive it develop nerve damage that cause pain, tingling, and long-term disability. There are currently no treatments that prevent this side effect. To understand why this nerve damage occurs, Dr. Gomez Deza and colleagues use cell models (derived sensory neurons that closely mimic how children's nerves respond to vincristine). Using a large genetic screen, Dr. Gomez Deza and team will use a molecular regulator that functions as a key switch helping drive nerve injury. Blocking this pathway protects nerve cells in the lab, reduces pain-related behaviors in models, and does not interfere with vincristine's ability to fight cancer. Dr. Gomez Deza and colleagues will uncover how this pathway controls the harmful stress responses triggered by chemotherapy and will test whether inhibitors already in clinical trials for other uses could serve as protective treatments for children receiving vincristine.