Grant: Collaborative Health Research Projects

Brain cancer is largely incurable and mostly untreatable. The most common form of brain cancer, malignant gliomas, arevery aggressive, resulting in patient survival of only a year after diagnosis. Present treatments for malignant gliomas largelyfail because cancer cells can rapidly invade surrounding brain tissue, resulting in recurrent tumors. We found that malignantgliomas overexpress a gene, DRR, which is a primary driver of their invasiveness, yet not expressed on normal glial cells.To stop the progression and recurrence of brain cancer, we propose to target DRR. We propose to selectively knock-downDRR with siRNA and to ensure specificity to cancer cells with targeting antibodies. We will deliver the siRNA, antibodies andchemotherapeutics in tiny beads polymeric nanospheres.The drug delivery system is comprised of innovative polymer nanospheres, which penetrate the brain tumor site.Nanospheres will deliver antibodies against brain cancer, chemotherapeutics and silencing RNA to knockdown DRR. Thespherical beads will degrade after releasing their payload in the cancerous tissue. This system of localized delivery isparticularly compelling for invasive brain cancers where the aggressive malignant/invasive glioma cells have spreadthroughout the brain and are not easily removed. The long-term goal is to clinically assess the efficacy of locally-deliveredtargeting RNA to block invasiveness in recurrent glioblastoma and extend median progression-free and overall survival inpatients.Our team has the complementary expertise required for success in the complex race to overcome brain cancer. Bycombining novel bioengineering strategies with innovative silencing approaches, targeting antibodies, and neurosurgery, theteam will provide a superb environment for training of HQP. In collaboration with our industry, science and clinical partners,we will advance knowledge to practical application, with the ultimate goal of defeating brain cancer.