Translating Venom to Medicine: A Comprehensive Review on the Role of Chlorotoxin in Glioblastoma Diagnosis and Therapy.

Glioblastoma (GBM), the most aggressive primary brain tumor, carries a dismal prognosis, with median survival remaining under 15 months despite standard therapies. This is largely due to the tumor's infiltrative nature, the restrictive blood-brain barrier (BBB), and intratumoral heterogeneity. Chlorotoxin (CTX), a 36-amino acid peptide derived from scorpion venom, has emerged as a promising multifunctional agent with high specificity for neuroectodermal tumors. In this comprehensive review, we highlight CTX's potential to address critical limitations of current glioma treatments by bridging diagnostic and therapeutic modalities. Diagnostic advancements include CTX-conjugated near-infrared fluorophores and nanoparticles for fluorescence-guided surgery and multimodal imaging, enhancing intraoperative accuracy. On the therapeutic front, CTX enables targeted delivery of siRNA, radioisotopes, and novel immunotherapies such as CTX-directed CAR T cells. We also examine emerging clinical data supporting the safety and preliminary efficacy of CTX-based interventions. Collectively, CTX represents a paradigm shift in neuro-oncology - offering a single molecule with both diagnostic and therapeutic capabilities. Its utility may also extend beyond gliomas to metastases and other malignancies within and beyond the central nervous system.