TMIC-40. A novel therapeutic strategy using a single non-toxic agent that produces consistent long-term control of orthotopic experimental glioblastomas

Abstract Based on conventional somatic mutation theory (SMT), the goal of cancer therapy is complete tumor cell eradication. In glioblastoma, this has proven very difficult to achieve without irreparably damaging normal tissue. We believe that the missing link to more effective treatment lies in increased attention to tissue healing and have been investigating a non-toxic compound that both eradicates tumor cells without damaging and perhaps strengthening normal ones. BPM31510 is a nanoparticle incorporating water insoluble oxidized CoQ10 into a lipid emulsion allowing delivery of supraphysiological levels of CoQ10. In a unique long-term in vitro coculture competition model, we noted that at the correct dosage, robust normal growth occurs while cancer cells are near or totally eradicated in three glioma/normal cell pairs from human, mouse and rat cell lines. In vivo, we can increase survival and in effect cure over 50% of animals treated in three different tumor models. Focusing on the C6 glioma model, where we can serially deliver iv BPM31510, cures were obtained in 100% at a dose of 400 mg/kg BPM31510. Notable in our in vivo studies was the observation that tumor size markedly increased on MRI in the early stages of administration, only to start shrinking after 2 weeks. During this time, rats do not appear ill. Therefore, in order to optimally use this medication in clinic, we will need non-invasive measurement tools and have noted that magnetic resonance spectroscopy (MRS) can detect major changes in the tumor environment, suggesting substantial metabolic reprogramming is occurring while the tumors are in the post-treatment growth phase. These findings demonstrate that BPM31510 has the capacity to be an effective, non-toxic agent with great clinical potential. We hypothesize that unlike most conventional anticancer agents that much of its effect results from its capacity to restore tissue homeostasis and enhance healing.