Watch Dr Briony Gliddon accept the research grant award and hear a bit about the project.
Project Summary:
Glioblastomas are lethal brain cancers with limited treatment options, and extremely poor patient outcomes. Thus, there is a desperate need for new therapies. Sphingolipids are molecules present in all cells that can control many of the key hallmarks of cancer. This includes control of cell growth, survival and migration, and new blood vessel formation. Thus, defects in the control of sphingolipids can drive tumour growth. Indeed, one of the key proteins that control sphingolipid levels, sphingosine kinase 2 (SK2), has been looked at as a drug target in a number of other cancers. This has led to an SK2 inhibitor entering phase 2 clinical trials for liver cancer. Little is known about SK2 in glioblastoma, but since sphingolipids are important in the brain we looked to see if SK2 could be a therapeutic target in this cancer. We found that SK2 is activated in glioblastoma, and that this is linked with poorer patient outcomes. Inhibiting SK2 kills glioblastoma cells, and genetic knockout of SK2 in glioblastoma cells dramatically reduces tumour growth. These findings suggest that SK2 is an attractive drug target for glioblastoma. Notably, mice that lack SK2 have no obvious problems, and SK2 inhibitors we will employ have passed phase 1 clinical trials for safety in humans. Thus, blocking SK2 appears safe. In this proposal we will test the effect of SK2 inhibitors against glioblastoma, using advanced pre-clinical models. Success in this work will drive clinical trials of SK2 inhibitors as a new therapy for glioblastoma.
Outcomes:
Dr Gliddon and her team’s previous mouse studies revealed the potential of SK2 inhibitors as a therapy for glioblastoma. In this project, they used advanced techniques (CRISPR/Cas9) to confirm these findings in patient-derived tumour cells – a crucial step towards clinical trials.
Their results strongly demonstrated that SK2 drives GBM tumour growth. They established that clinically relevant SK2 inhibitors can block the growth of patient-derived tumour cells, and notably that this can enhance the potency of a type of chemotherapy called temozolomide (TMZ). Furthermore, Dr Gliddon’s team found that SK2 inhibition could be a viable treatment for recurrent GBM, which currently has no standard treatments.
For patients and families, these findings represent meaningful progress toward the development of more effective therapies and improved survival outcomes for those with glioblastoma.
You can read more about these research results in the final report, linked below.
The Brain Foundation is dedicated to funding the next generation of Australian research into brain disorders, diseases, and injuries, with the ultimate goal of advancing diagnoses, treatments, and patient outcomes.