Developing a metabolic roadmap to discover novel therapeutic avenues to starve GBM
Glioblastoma (GBM) is the most aggressive primary brain tumour with an overall survival prognosis of less than 15 months - a devastating diagnosis for both the patient and their family. Over many years, researchers have tried to map the genetics of the disease, in order to determine new ways to treat GBM based on genetic changes such as mutations. Despite this, there remains no effective treatments for GBM, with surgery, chemotherapy and radiation therapy the current options, suggesting we need to try an alternative avenue.
While genetic changes in the DNA have a profound effect on cancer cells, these effects are actually carried out by proteins which the DNA codes for. In turn these proteins, including nutrient transporters and enzymes, combine together to mediate the uptake and metabolism of nutrients in order to facilitate the rapid growth of the cancer cells. This is critical, as a cancer cell needs to essentially double all its DNA, RNA, proteins and fats in order to make two new cells during cell division. This cell division occurs rapidly in GBM, increasing the size of the tumour and ultimately tumour relapse post-treatment.
In this pilot study, we will undertake metabolic profiling of GBM patient samples taken at surgery, to understand how they use and distribute their essential nutrients. This will develop a metabolic roadmap which can be combined with genetic information being developed through the Cancer Genomics – The Next Level project. Ultimately, success in this project will enable us to understand how GBM tumours are metabolically programmed, providing the critical data for future studies developing new therapies targeting these metabolic vulnerabilities. These future studies would include using our patient-derived laboratory models to test currently available metabolic drugs, thereby determining whether they can successfully starve the GBM cells.