Modulation of STING to enhance the efficacy of treatments for diffuse midline glioma
Pediatric diffuse midline gliomas (DMG) are devastating brain tumors. DMGs account for up to 10% of pediatric brain tumors and are uniformly fatal. The standard of care for DMG generally consists of radiation therapy (RT). Survival rates have not improved for at least two decades. New treatments are urgently needed to improve survival for DMG patients. Our study investigates highly therapeutically relevant molecular processes to inform future combination treatment strategies. The current studies will determine if future clinical trials should be focused on drugs that target STING. STING is an important part of the human immune system. Drugs that target STING have already entered clinical trials for other cancer types. Therefore, the current studies will determine if these new drugs should be investigated in clinical trials in children with DMGs.
The results will help us to design many aspects of such future clinical trials, including (i) the ideal timing of the different treatments such as radiation therapy (RT) and new drug therapies, (ii) the most efficacious types of new drug therapies to explore, (iii) the appropriate patient inclusion criteria for future clinical trials, (iv) biomarkers of response to be monitored on trial, and (v) appropriate correlative studies to design along with the trials. We believe that thoughtful combination treatment approaches guided by our results will be needed to maximally improve DMG outcomes and bring us closer to a cure for DMG. Specifically, we investigate RT which is routinely used for children with DMG, both at the time of diagnosis and also sometimes when the DMG comes back. Thus, the findings here will be immediately actionable by guiding which types of new treatments should be pursued alone or in combination with RT in future clinical trials for DMG.
