Watch Dr Stanley Stylli accept the research grant award and hear a bit about the project.
Project Summary:
Each year, approximately 2000 Australians are diagnosed with brain cancer and approximately 1600 will die from this disease. Glioblastoma (GBM) is the most common form of brain cancer and it is the most aggressive and lethal primary brain tumour due to its highly invasive and neurologically destructive nature. The current clinical approach involves surgery, radiotherapy (RT) and chemotherapy with temozolomide (TMZ) resulting in a median survival of approximately 15 months and a poor 5-year survival rate of only 4.6%. During this treatment, changes can occur in the GBM cells allowing them to survive multiple rounds of treatment. Our unique approach involves the generation of patient derived GBM cells that have survived multiple rounds of RT/TMZ treatment designated as ‘treatment resistant cells’ (long term treated). This project will examine the genetic fingerprint of untreated, single treatment and long term treated cells providing a comprehensive overview of the RT/TMZ treatment response versus genetic fingerprint before being treated with adjuvant therapies. This project will utilize a number of FDA-approved drugs that we have previously determined as potential agents for targeting GBM cells, as a single drug or in a ‘polytherapeutic combination’ repurposing approach to reduce the viability and invasive capacity of the different GBM cell groups. Determining the most effective adjuvant drug treatment especially against the ‘long-term treatment resistant’ GBM cells and correlating this with their genetic fingerprint will allow us to potentially determine which patients in the future may respond to this treatment when used post-RT/TMZ treatment.
Outcomes:
Dr Stylli’s team found that polytherapeutic approaches were better at killing GBM cells than just using one drug, and the most effective approach was the combination of all four drugs. This was true even for the cells that were resistant to radiation (RT) and TMZ. The effect was even more pronounced when the four drugs were used in combination with RT and TMZ.
They also developed a better understanding of GBM genetics. The researchers then looked at information from a large study of GBM patients. They discovered that when the genes targeted by the four drugs were expressed in the tumours at high levels, patients tended to do worse. This suggests that the drug combination is attacking the right targets.
This study is an important step towards finding better treatments for this deadly disease and offers hope for future breakthroughs.
Outcomes submitted October 2024.
The Brain Foundation is dedicated to funding the next generation of Australian research into brain disorders, diseases, and injuries, with the ultimate goal of advancing diagnoses, treatments, and patient outcomes.