Improving therapy in glioblastoma multiforme by activating complimentary programmed cell death pathways

• Honours
• PhD

Glioblastoma (GBM) is the most common and aggressive form of brain cancer. The mechanisms underlying GBM tumour formation are complex, however, evasion of programmed cell death (PCD) is a common feature of this malignancy, contributing to tumour formation.
This novel project seeks to identify new medicines that activate different PCD pathways, such as apoptosis and ferroptosis, that may be used on their own or in combination with the standard of care agent, Temozolomide, to treat GBM.The project also aims to decipher the role of autophagy, another mode of PCD in GBM in order to uncover new treatment approaches. Using various methodologies, such as flow-cytometry based assays, RNA-sequencing, patient-derived tumour cell culture models and in vivo models of GBM, overall, we aim to delineate better treatment strategies for GBM patients.

Our lab focuses on exploiting programmed cell death pathways, such as apoptosis, ferroptosis. and autophagy to develop novel and improved therapies for GBM and other cancers. A substantial interest in our lab is the use of BH3-mimetic drugs; these are small molecule compounds designed to activate apoptosis PCD signaling. We have previously shown that the combination of BH3-mimetic drugs with current standard of care chemotherapy and small molecule inducers of the ferroptosis PCD pathway can potently kill GBM cells (Moujalled Cell Death Differ 2022, doi:10.1038/s41418-022-00977-2). We have national and international collaborations to investigate potential new therapies for GBM and utilise brain cancer patient-derived neurosphere cultures and in vivo models of GBM to evaluate the clinical potential of emerging therapies.