Glioblastoma (GBM) is an aggressive brain cancer that resists to conventional treatment with radiation and chemotherapy, mainly due to glioblastoma stem cells (GSCs). GSCs possess unique features to sustain their multiplication and initiate a tumor able to quickly proliferate and invade other areas in the brain. GSCs account for tumor resistance to radiation and chemotherapy and act as a disease reservoir for tumor recurrence, making them difficult to eliminate. 

GSCs adapt the two major cellular antioxidant systems, thioredoxin and glutathione to decrease oxidative stress, to repair chemotherapy and radiation-induced damage and to survive. Our research group leveraged the rationale to co-target the thioredoxin and glutathione antioxidant systems to overwhelm and kill GSCs. Our research group discovers a new combination using Auranofin (drug that blocks thioredoxin reductase), and Piperlongumine (natural compound that targets the glutathione system), very effective to kill these GSCs.   

The triple combination of Auranofin and Piperlongumine with Radiation killed both GSCs and glioblastoma cells that form the tumor bulk much more effectively compared to each treatment alone.  

Further validation of these exciting findings in an animal model is required to advance this triple combination therapy into a clinical trial. Combining Radiation with Auranofin, a well-tolerated drug clinically approved for treating rheumatoid arthritis with a natural product Piperlongumine with a known safety profile to inhibit the glutathione system will enable us launching a phase II clinical trial in newly diagnosed GBM patient. This novel treatment has the potential improving patient survival by making GBM tumors more responsive to current treatments.