Funded Grants

SEED GRANT

Grantee: Duke University
Project Lead: Yiping He, PHD
Grant Title: Sirpiglenastat for treating glioblastoma
Program Area: Glioblastoma
Grant Type: UKF Seed Grant
Year Awarded: 2024
Amount: $50,000
Duration: 1 year

Summary: Glioblastoma is a highly aggressive and deadly brain cancer because the tumor cells quickly become resistant to treatments like chemotherapy, radiation, and immunotherapy. This resistance happens because the tumor cells adapt to therapies that aim to kill them, and they also create an environment that weakens the immune system's response. A key group of molecules called purines, which serve as building blocks and energy sources for cells, plays a major role in these processes. Normally, tumor cells get purines by both recycling them and making them from scratch. However, about 50% of glioblastoma cases involve a genetic mutation that stops the tumor cells from recycling purines, making them entirely dependent on producing purines from scratch. This means that blocking this purine production could be an effective way to treat these cases. Our prior research showed that blocking purine production can work in glioblastoma animal models, but the drug used was too toxic for clinical use. Recently, we have discovered that a new, lower-toxicity prodrug - originally intended to treat prostate cancer in our research - can effectively inhibit purine production from scratch. We confirmed that this strategy not only directly attacks the prostate cancer cells but also boosts the immune system's ability to fight the cancer, leading to better results with fewer side effects in animal models. Subsequent preliminary studies suggest that this prodrug could also be effective in treating glioblastoma by killing tumor cells and reducing their ability to suppress the immune system. This project aims to further test the prodrug in different glioblastoma models to determine its effectiveness, with the hope of developing a new treatment strategy that could improve outcomes when combined with existing therapies in about half of glioblastoma cases.