Glioblastoma (GBM) is the most common & aggressive brain tumor having dismal prognosis. Patients diagnosed with the disease have a median survival of about 15 months only. Current mode of therapy is limited to surgical removal of the tumor and routine chemo/radiotherapy. However, emergence of chemo/radio resistance, and tumor recurrence is common. There is a pressing need for devising novel, multimodal therapies. miRNA based therapies hold promise for cancer treatment owing to their multi-pathway targeting abilities. Our study focuses on two oncogenic miRNAs: namely, miR-196a and miR-210, both associated with GBM progression and aggressive phenotype. Our work (at IITD) on these two miRNAs show that both of these are hypoxia induced and function as oncogenic miRNAs by promoting cellular proliferation and migration and inhibit apoptosis and are also associated with poor patient survival. Although miRNA therapy sounds attractive, the major bottleneck is their delivery as in naked form they are susceptible to degradation by nucleases, clearance by the reticuloendothelial system etc. Dr.Popat’s laboratory at UQ has recently prepared ultra-small silica nanoparticles which has potential to cross BBB and accumulate specifically in tumour microenvironment and deliver genetic molecules. By combining these two innovative technologies (micro RNA and nanoparticles) we will provide proof-of-feasibility and efficacy of new therapeutic strategies aimed at reversing the immune evasive capability of Glioblastoma. The work will involve synthesis and characterization of the nanoparticles, their ability to deliver anti-miRNAs to the cells will be checked along with its efficiency to inhibit levels of said miRNAs. Upon successful inhibition of the above miRNAs with co-delivery of anti-210 and anti-196a by the NPs to GBM cells, the effect on the different cancer hallmarks will be checked. After completing the cell-based studies, we would test the efficacy of this therapy in an orthotopic mouse model of GBM.
Glioblastoma is a highly aggressive, incurable cancer with uniformly poor outcomes for patients diagnosed with primary tumours (5-year survival rate <50% in adolescences). Affected patients suffer devastating impact on their quality of life, with symptoms including headaches, nausea and vomiting, seizures, changes in sensation, personality and mood and venous thromboembolism, leading to further complications. Available therapies, have only modest impact on the course of disease progression and nearly all patients will relapse. The proposed research aims to improve the quality of care and quality of life for glioblastoma patients by developing new, potentially curative therapies. In addition to killing primary tumours, this class of therapy has the potential to prevent recurrence, which is what ultimately kills most brain tumour patients. Our research pioneers the use of two novel strategies to induce powerful anti-tumour responses. Importantly, both of these strategies are well differentiated from the therapies that are currently being developed for brain tumours. As a result, the strategies we are developing may provide treatment options for patients who fail to respond to other drugs. Furthermore, our approaches are complementary to the major pipeline therapies and therefore have the potential to be used, eventually, in combination with other immunotherapy agents to induce synergistic effects and further improve treatment outcomes. Finally, the new therapies have the potential to provide superior safety and side-effect profiles to existing treatments, thereby reducing the impact of therapy on patients quality of life.