Glioblastoma Multiforme (GBM) is the most malignant brain tumour and persists in having a poor survival of 12-15 months despite current best therapies that include maximal safe surgical resection, radiotherapy and chemotherapy. These aggressive tumours are synonymous with recurrence and are defined by their ability to diffusely infiltrate and invade normal brain parenchyma. GBM recurrence is now thought to be attributed to the presence of a sub population of treatment resistant cells with stem like properties termed glioma stem cells (GSCs). Conventional therapies are ineffective at targeting these cells and new therapeutic targets and treatments are needed to target these cells and improve patient outcomes.
One potential target, due to its participation in a wide variety of oncogenic processes, is Dynamin II (Dyn II). Dyn II has been reported to support tumorigenesis, cytokinesis and cancer cell migration and invasion in multiple cancers. This study found that novel Dynamin II inhibitors, Dyn34-2 and CyDyn4-36 were able to inhibit cell proliferation in glioma cell lines and induce cytotoxicity in glioma stem cells. In addition, the extent of effect was also compared to the current drug used in clinical treatment of GBM, Temozolomide, and the results greatly surpassed that of TMZ. Inhibition of dynamin II via these novel compounds also decreased the migratory ability of both glioma cell lines and glioma stem cells, which infers potential to improve patient outcomes by inhibiting infiltration into normal brain which results in recurrent tumours. Current experiments are underway to determine if treatment with dynamin II inhibitors in a glioma stem cell driven in vivo model of GBM, is able to reduce tumour burden in mice. Overall, dynamin II appears to be a promising target and its inhibition remains a potential therapeutic avenue.