Meningioma is one of the most common central nervous system (CNS) tumors, comprising around 38.3% of all primary brain tumors. It is derived from the meningothelial cells in the brain or spinal cord. Currently, the standard of care for meningiomas is maximum safe surgical resection, succeeded by adjuvant radiation in some cases. Systemic therapy is used as salvage therapy in the case of meningiomas that have become refractory. To date, there are no targeted systemic therapies for meningioma, and many are still in clinical trials. There is, thus, a pressing need to understand the molecular biology of meningioma pathogenesis and devise novel therapies. Gene/miRNA-based therapies hold promise for cancer treatment due to their ability to target multiple pathways. Our study focuses on developing gene/miRNA based nanotherapeutics for meningioma.
Our work (at IITD) aims to identify the candidate gene/miRNA involved in meningioma pathogenesis and study their functional role in cancer- analysis of cell cycle, cell proliferation, migration, apoptosis, etc. Delivery of gene/miRNA therapy in naked form can make them susceptible to degradation by nucleases, clearance by the reticuloendothelial system, etc. Dr.Popat’s laboratory at UQ has recently prepared metal organic framework (MOF) nanoparticles which have the potential to accumulate specifically in tumour microenvironment and deliver genetic molecules. A combination of these two innovative technologies (microRNA and nanoparticles) will provide proof-of-feasibility and efficacy of new therapeutic strategies for Meningioma treatment. The work will involve synthesis and characterization of the nanoparticles, their ability to deliver siRNA/miRNAs to the cells will be checked along with its efficiency to inhibit levels of candidate miRNAs. Upon successful inhibition of the candidate miRNAs by the NPs to Meningioma 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.
Meningioma is amongst the most commonly occurring central nervous system (CNS) tumors, while the current treatment options are only limited to surgical resection and radiation therapy. These treatment options are invasive and can be limited due to factors, like, tumor location. There is no targeted systemic therapy currently available for meningioma. Thus, there is a dire need to thoroughly understand the molecular biology of meningioma pathogenesis and find new therapeutic targets. The proposed research aims to improve the quality of care and quality of life for meningioma patients by developing new, potentially curative therapies, specially for high grade and recurrent meningiomas that have become refractory to conventional treatments. In addition to killing primary tumours, this class of therapy also has the potential to prevent recurrence, which is what ultimately kills most brain tumour patients.
Our research pioneers the use of two novel strategies, which are well differentiated from the therapies that are currently being developed for CNS tumours and can induce powerful anti-tumour responses. The strategies we are developing may provide novel treatment options for meningioma patients. 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.