Treating Aggressive Brain Tumors with the Combo Bumetanide/Mebendazole: A New Cytotoxic, Anti-Invasive Network Strategy

Despite much progress in aggressive brain tumors, we are still failing to provide efficient cure.This is due to the complexity of brain tumors, their heterogeneity& plasticity, and the neglected peritumoral microenvironment generated hyperactivity that facilitates metastasis.We have tested the effects of a combo of 2 anticancer drugs that associate anti-invasive therapy and cytotoxicity.Bumetanide (Bum) is a NKCC1 sodium-potassium-chloride cotransporter inhibitor that restores brain inhibition & blocks hyperactivity.Mebendazole (Meb), is a repositioned anti-helminthic drug with vincristine-like cytotoxic effects that attenuates Glioblastoma in human and experimental animals.The combo efficiently reduced migration and produced massive neuronal apoptosis in our preclinical study.Here, we report the results of a compassionate pilot case performed in an inoperable brain metastatic breast cancer patient after failure of radio-chemotherapy, Herceptin and approved targeted therapies.The patient received 1mg/day and Meb at 200 mg three time a day without any side effect.The combo rapidly reduced cortico-therapy, tumor size, motor deficit and diplopia during the 7 months of treatment.A rigorous trial is mandatory to progress: Our trial will associate Bum at in newly diagnosis pharmaco-resistant glioblastomas, invasive meningiomas and brain metastasis.This may pave the way for the first anti-invasive tumor microenvironmental modulating therapy in oncology, supporting a major new pharmaceutical market.