A Phase II Study of Adding Flubendazole to Standard Concurrent Chemoradiotherapy With Temozolomide in Patients With High-Grade Glioma

High grade glioma is the most common and lethal primary brain cancer, arising from glial stem cells . It is characterized by rapid growth, and a poor prognosis .Despite an intensive standard-of-care therapeutic approach combining surgical resection, radiotherapy, and chemotherapy with Temozolomide (TMZ) , survival rates remain low, with an almost inevitable recurrence . The median overall survival is only 12 to 15 months after diagnosis .Despite this scenario, no significant therapeutic advances have been recorded in the past 20 years. Innovative approaches such as tumor-treating fields, immunotherapies, and stem cell-based therapies have reached clinical trials, but clinical benefits remain limited . Therefore, there is an urgent need to identify new strategies to overcome the resistance of this type of cancer. A key contributor to treatment failure is the pronounced cellular heterogeneity of glioma, which resembles the complexity of a developing organ and contains cells with stem-like properties.There are a therapeutic agents that inhibit mitochondrial biogenesis also include antibiotics, anthelmintics, and antimycobacterial drugs. Flubendazole (FLU) is a member of the benzimidazole group, a drug commonly used in veterinary and human medicine for its anthelmintic properties. This anthelmintic effect is based on its ability to bind to β-tubulin, which causes inhibition of tubulin polymerization leading to microtubule disruption and loss of function . These effects are thought to be mediated not only via microtubule disruption but also via interference with several signaling pathways, including IL/JAK/STAT3, AKT, NF-κB and others, ultimately to cell cycle arrest, autophagy, apoptosis and/or other types of cell death .