The Innovation Grant aims to fund new research projects that
deviate from existing paradigms and current lines of investigation. The grant
allows investigators to follow leading observations and exploration of novel
ideas in brain cancer research. The grant supports investigators to produce
proof-of-concept data for their higher-risk projects and establish feasibility
for future research and grant applications.
The Innovation Grant in aid will offer up to $200,000 over 2
Australian National University, ACT - $200,000 (2017)
Uncovering novel drug targets to treat primary brain cancer
Treatment strategies for patients with invasive brain tumours are currently based on the World Health Organization (WHO) tumour grading system. This system does not account for differences within tumour types, although these can significantly affect treatment outcomes. This grant focuses on the second most common primary brain cancer in adults, Oligodendroglioma. Although patients with this class of brain cancer have a median survival of 15 years, this prolonged disease is associated with considerable suffering, including seizures and major neurological deficits. Of major concern are observations that although the current palliative treatment regime for Oligodendroglioma does not alter tumour grade in most patients, in a subset of patients (around 15 per cent) the recurring tumours become extremely aggressive and actually hasten death for reasons currently unclear. This project aims to identify new prognostic markers and investigate drug therapies for specific Oligodendroglioma tumour types based on their molecular signature. These studies will lead to more individualised treatments, which is critical to improving survival and quality of life for brain tumour patients.
Mixing old treatments with new drugs to cure brain cancer
Brain cancers kill more young people in Australia than any other disease. Nick Gottardo's work will focus on the most common malignant brain cancers in children and adults, to improve survival rates. His research aims to find approaches that enhance existing treatments, prove the new methods work using laboratory techniques, then translate them into clinical trials.
Radiation treatment works by damaging the DNA inside cancer cells, causing the cells to die. However, cancer cells often repair the DNA damage, survive, and multiply, leading to treatment failure and cancer regrowth. He has evidence radiation therapy can be improved if DNA repair is stopped.
He will study two drugs that stop DNA repair. Called iCHK and iATR, these drugs work by blocking proteins in the cell called CHK and ATR. When DNA is damaged, CHK and ATR normally work to repair DNA, allowing cancer cells to survive. But in the presence of the drugs, DNA repair is stopped, and the cells die. This works better in cancer cells than healthy cells because cancer cells multiply faster.
He aims to prove that iCHK and/or iATR enhance the ability of radiation to kill brain cancer cells, without causing damage to healthy brain tissue. For this, he will create "avatars" of brain cancer in the lab by growing the cancer cells in mouse brains, then give them each new drug together with radiation.
A/Prof Gottardo expects to see decreased cancer growth and increased animal survival as measures of success. To measure safety, he will examine the animals for side effects.
His results will determine if iCHK and iATR have can improve the effects of radiation, which in turn should reduce the chances of the brain cancer relapsing. This will lead to new clinical trials, and help achieve more cures and better quality of life for patients.
University of Queensland, QLD - $200,000 (2017)
Powering and arming the immune system to combat Glioblastoma
Glioblastoma is the most common and most aggressive type of brain tumour. Available therapies aim to slow cancer progression and relieve symptoms, but are unable to cure the cancer or to substantially improve the patient's quality of life for very long.
A new type of cancer treatment, called "immunotherapy", stimulates patients' immune system to fight their cancer. The first immunotherapies were recently introduced into medical practice and have already demonstrated the ability to shrink and sometimes eliminate several types of advanced cancers that were previously considered untreatable, including Glioblastoma (GBM), although the clinical benefit is still limited to a fraction of patients.
Dr Mazzieri's proposed research investigates strategies to harness the power of immunotherapy to improve glioblastoma treatment. The main obstacles limiting the efficacy of immunotherapy against glioblastoma are (i) that the cellular environment within the tumour contains signals that actively suppress the activity of immune cells and (ii) that some types of tumours, including glioblastoma, are poorly "immunogenic", meaning that they lack signals to make them visible to immune cells.
This research will investigate new and innovative approaches to overcome these obstacles and thereby improve the outcome of immunotherapy for glioblastoma. To combat suppression of immune activity, Dr Mazzieri will use genetic engineering technology to reprogram a class of cell (which normally inhibits immune cells) to produce a powerful immune stimulant within glioblastoma tumours. Moreover, to make glioblastoma tumours more visible to the immune system, she will apply a technique to kill tumour cells in a manner that causes them to release powerful immune-activating signals. clinicians will then deliver these immune-activating signals to the patient using new nanotechnologies developed in Dr Mazzieri's laboratories.
This research has high potential to identify new treatments for glioblastoma with the ability to substantially prolong quality survival and possibly even cure some patients.
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