| Project title | Cure for Life Chair in Neuro-Oncology Fund |
|---|---|
Grant Amount | $2.56 million |
Institution | UNSW |
Investigator Team | Principal investigators A/Prof. Kerrie McDonald with associate investigators |
Grant Type | Infrastructure |
Years | 2009 – 2014 |
The Cure for Life Chair in Neuro-Oncology Fund will support brain cancer research at the Cure for Life Neuro-Oncology Lab, led by A/Prof. Kerrie McDonald at the Lowy Cancer Research Centre.
The lab specialises in:
- Defining drug-diagnostic combinations where the presence of a molecular target or marker identifies who are most likely to respond to a specific therapy.
- Culturing and growing patient specimens in real-time to foster a “personalised medicine” approach utilizing patient derived xenografts (PDX) models. With time, the group hopes that they can report back to the clinicians with drugs and drug combinations that have reduced tumour size in the lab, and translate these findings to patients.
- Working with clinical trial groups and consortiums to identify “responders” to the treatment and better understand the underlying biology.
- Developing a better understanding of the mechanisms of cancer resistance.
Through their work, they aim to achieve new and more targeted treatments to improve survival times.
“Personalised medicine is a significant goal of the lab – that is, to match the right treatment to the patient.”
A/Prof. Kerrie McDonald
Progress: Final report (2014)
The Patient Derived Xenograft (PDX) models are the core strength of the Cure Brain Cancer Neuro-Oncology Group. We have established 23 patient derived cell lines to enable the in vitro screening of novel treatments for Glioblastoma and all 23 tumours have shown tumourigenicity in athymic mice. The tumours grown in the mice show significant resemblance to the original tumour, with the heterogeneity preserved allowing the greatest accuracy to determine the clinical efficacy of novel therapeutics. This provides us with an excellent preclinical model and greater confidence that when we test the drugs, and it works, it will work in patients.
We investigated the roles of DNA repair pathways in temozolomide resistance by studying their mRNA and protein expression in pre and post-treatment samples. When the specimens were evaluated individually, trends in mRNA expression levels that were associated with survival were evident. This body of work has contributed to understanding the mechanism behind resistance.
The development of new, active and potentially targeted drugs for the treatment of GBM represents a major unmet need. In this study, we investigated the drug veliparib on a panel of primary and recurrent GBM cell lines derived from patients. We also examined the efficacy of veliparib on temozolomide-induced resistant cell lines to determine the suitability of veliparib as a second line chemotherapy once failure to temozolomide is evident.
Since adjuvant radiotherapy significantly reduces the mortality and increases median survival in patients with GBM, the radioresistance of GBM cells and targets to modify their radiation tolerance are of significant interest. High glycolytic states of tumour cells are known to correlate strongly with radioresistance. Dichloro-acetate (DCA), currently being used to treat lactic acidosis, can modify tumour metabolism by activating mitochondrial activity to force glycolytic tumour cells into oxidative phosphorylation. This study provides the proof of concept that DCA can effectively sensitise GBM cells to radiation by modulating the metabolic state of tumour cells.