Developing novel P2X7R inhibitors for treatment of glioblastoma

Glioblastoma is the most aggressive form of primary brain cancer. The average life expectancy is only 12-18 months and in the last 20 years, the 5-year survival of patients with glioblastoma has not significantly improved, currently at ~7.1%. Due to the aggressive and highly infiltrative nature of this cancer, treatments that can combat the cancer cells highly proliferative and invasive capacity are needed. Our work has identified that P2X7R is a potential therapeutic target in the context of glioblastoma. P2X7R is a purinergic ATP sensing receptor and is over expressed in cancer cells compared to surrounding cells. It plays significant roles in tumour cell proliferation, migration and invasion, and has demonstrated these roles in glioblastoma specifically. In this project, we will be testing various pharmacological agents (anti-P2X7R compounds) in a combination of cancer cell lines, organoids, patient derived glioblastoma cultures and potential patient derived monocytes. The small molecules will be tested to characterize their anti-P2X7R capabilities and their subsequent anti-tumour capacity. This study will help inform extension of the findings into future human clinical trials of a novel anti-P2X7R compound for treatment of glioblastoma