Fisetin in malignant nervous system tumors: molecular insights and translational advances

Malignant tumors of the nervous system, such as gliomas, medulloblastomas, and neuroblastomas, pose a greater clinical challenge due to their aggressive and invasive nature and their resistance to current treatment options. The blood-brain barrier (BBB) impairs the delivery of therapeutic agents, which is associated with poor prognosis. The natural flavonoid fisetin has demonstrated potential for cancer treatment by regulating major cancer-related signaling pathways, including PI3K/Akt/mTOR, NF-κB, and MAPK. Preclinical studies suggest that fisetin induces apoptosis, suppresses tumor invasion, and reduces malignancy in glioma, medulloblastoma, and neuroblastoma models. However, evidence for fisetin’s effectiveness remains preclinical and in vitro, with no clinical trials in humans to date. One solution to this challenge is to use nanotechnology-based delivery systems to increase fisetin’s stability and solubility and facilitate its crossing of the BBB, thereby enhancing its therapeutic efficacy. Such advancements have made fisetin a promising option for neuro-oncology treatment. Further clinical trials are needed to assess the safety, efficacy, and effectiveness of fisetin in combination therapies. When conjugated with nanotechnology-based delivery, fisetin may enable a digital transformation in treatment outcomes for patients with malignant nervous system tumors.