In glioma cell lines, NO-Cbl synergized with TRAIL and temozolomide (TMZ) (combination index < 1.0), enhancing antiproliferative effects and suggesting potential to overcome resistance mechanisms.<h4>Conclusion</h4>This pilot study demonstrates that NO-Cbl crosses the BBB, accumulates selectively in brain tumor tissue, and synergizes with established and experimental glioblastoma therapies. This evidence concerns the gene CBL and brain neoplasm.