Glioblastoma is a rare, aggressive, brain tumor that is difficult to treat. It originates from brain cells known as glial cells, which support brain tissue and the spinal cord. Glioblastoma commonly affects older adult males (45 – 70 years old) with various associated risk factors including hereditary mutations and radiation exposure. Symptoms include headaches, seizures, personality shift, and difficulty with speech and motor skills. Diagnosis typically occurs when the tumor is late-stage due to its rapid progression. Unfortunately, after tumor resection and robust therapeutic treatment, tumors still recur. The average survival time after diagnosis is roughly 10 to 13 months and fewer than 10% of patients survive longer than 5-years. Scientists are currently working to improve treatment therapy and prolong patient survival.
A recent article in the Proceedings of the National Academy of Sciences (PNAS), by Dr. Alexander Stegh and others, developed a noninvasive form of therapy to treat glioblastoma. The team developed nanoparticles to deliver cancer treatment to the brain through nasal drops. Stegh is Professor and Vice-Chair of Research in the Department of Neurosurgery. He is also the Research Director of the Brain Tumor Center at The University of Washington St. Louis Medical School. Stegh’s work focuses on optimizing brain cancer therapy in patients with late-stage glioblastoma. Specifically, he investigates the genetic programs that underly glioblastoma to better engineer novel combination therapies.
Stegh and his team used nasal drops to deliver therapy and found that it elicited a strong immune response in mice with glioblastoma. This is a major breakthrough in brain cancer research. Researchers engineered nanostructures called spherical nucleic acids to activate immune cell pathways in the brain to recognize and target tumor cells. This method of delivery via nasal drops helped reach the tumor, which is commonly difficult to access.
The pathway the team activated is known as the stimulator of interferon genes (STING) pathway. This specifically activates an immune response after detecting foreign DNA in the cell’s cytoplasm. Previous work shows that STING activation can prime the immune system to target glioblastoma, but drugs used to elicit this activation breakdown quickly and have to be delivered directly to the tumor to have an effect. Since this form of treatment needs sustained exposure to the tumor site, invasive procedures are necessary. Stegh and others have minimized these invasive procedures by developing nasal drops as a platform to deliver treatment.
The engineered spherical nucleic acids were designed with gold cores studded with pieces of DNA that would trigger STING. While treatment through the nose has been developed, no nanoscale therapy has been tested with nasal drops. When the team treated tumor-bearing mice they found that the drug went directly to the tumor and reduced unnecessary side effects. Scientists then combined this nasal spray with other immunotherapies and found prolonged antitumor immunity.
Stegh and others successfully developed an immunotherapy that elicits robust and sustained efficacy against brain tumors. Scientists hope to move this to the clinic to improve patient outcomes. By developing an effective delivery system of STING agonists, researchers can sensitize glioblastoma tumors to other forms of therapy and further enhance cancer treatment.
Article, PNAS, Alexander Stegh, The University of Washington St. Louis Medical School