Gliomas are the most prevalent brain tumours and predominantly arise from glial cells. The World Health Organization (WHO) grades gliomas on a scale of I to IV, reflecting their degree of malignancy. The higher the grade the more severe the tumour in terms of growth and invasion. Grade I tumours are benign and can be cured while grade IV gliomas (also called Glioblastoma or GBM) are very aggressive forms of brain cancer.
Patients with GBM are among the most disadvantaged cancer patients in the healthcare system. The overall survival outcome for GBM is dismal with a median survival of 15 months. Standard GBM management typically involves surgical resection followed by radiotherapy and adjuvant chemotherapy with temozolomide (TMZ), but relapses usually occur within a month after initiating treatments.
The difficulty in effectively treating GBM patients is largely due to a fast-growing malignancy, providing several hindrances to understanding the molecular mechanisms underpinning disease progression and thereby constraining suitable therapeutic development. We have identified a unique requirement for lipid metabolism to support GBM malignancy and show in preclinical models that blocking lipid metabolism slows GBM growth. In this study, we will uncover novel proteins that are requisite for aberrant lipid metabolism and that confer a survival advantage in glioblastoma. Outcomes of this work range from elucidating in-depth mechanisms of tumorigenesis to conducting preclinical translational research. This will provide a rich resource to guide the genesis of a new class of metabolic-based drug for clinical treatment of glioblastoma patients.