Identification Of Biomarkers Predictive Of Response To Bevacizumab In Patients With Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$32,628.00
Summary
Despite multimodality therapy, the median survival for patients diagnosed with high grade malignant brain tumours is only 12 months. Patient response to therapy is highly variable. Our aim is to develop a “genetic signature” that will predict response to bevacuzimab (an agent targeting blood vessel formation). Identifying patients who will respond to bevacuzimab will save many patients from a toxic and costly therapy, from which they will derive little benefit.
Epigenetic Predictors Of Outcome In Malignant Glioma
Funder
National Health and Medical Research Council
Funding Amount
$697,720.00
Summary
Human high grade gliomas (HGG) present as heterogeneous disease, primarily defined by the histologic appearance of the tumor cells.Glioblastoma multiforme (GBM) is the most common illness and continues to have a very poor prognosis, despite the use of multimodality therapy including surgery, radiation therapy and chemotherapy. We will use our existing biobank of specimens, clinical information and molecular investigation to identify factors that determine outcomes.
Cancer arises through a combination of common DNA mutations which are associated with very poor survival in certain cancers. However, the cause of these mutations was always believed to be external factors (eg. UV light, toxins), Our exciting preliminary results show internal molecules, called circular RNAs, can drive these mutations and this project will investigate how this occurs and study whether targeting these molecules can reduce the incidence of cancers.
Identification Of Novel Epigenetic Modifiers Involved In Neural Stem Cell Function And Glioblastoma
Funder
National Health and Medical Research Council
Funding Amount
$748,680.00
Summary
The brain is produced from stem cells that have the capacity to make all the mature cells in the brain, both during development, and after injury. Brain stem cells are of interest due to the therapeutic potential to alter their function for regenerative medicine or treatment of neurodegenerative disorders. These stem cells also have characteristics in common with brain tumour cells. We seek to identify genes important in brain stem cells and brain tumours, in order to identify new targets for th ....The brain is produced from stem cells that have the capacity to make all the mature cells in the brain, both during development, and after injury. Brain stem cells are of interest due to the therapeutic potential to alter their function for regenerative medicine or treatment of neurodegenerative disorders. These stem cells also have characteristics in common with brain tumour cells. We seek to identify genes important in brain stem cells and brain tumours, in order to identify new targets for therapy.Read moreRead less
A 2:1 Randomised Phase II Study Of NivolUmab And Temozolomide Vs Temozolomide In Methylated Newly Diagnosed Elderly Glioblastoma (NUTMEG)
Funder
National Health and Medical Research Council
Funding Amount
$1,608,845.00
Summary
Radiotherapy and Temozolomide (TMZ) chemotherapy treatment for the brain tumour glioblastoma (GBM) is not as effective in elderly patients. If their tumour has a genetic marker called "methylated MGMT", TMZ does work relatively better and is often given alone. Elderly GBM patients with this marker will be randomly selected in this trial to have TMZ alone or TMZ + Nivolumab - a drug that assists the immune system to attack cancer.
TARGETING A NOVEL DNA-DAMAGE SIGNALING PATHWAY TO TREAT GLIOMAS
Funder
National Health and Medical Research Council
Funding Amount
$97,783.00
Summary
Glioblastoma Multiforme (GBM) is a high grade brain tumour for which current treatment modalities are inadequate. Tumour recurrence is almost inevitable and average life expectancy is measured in months. We have identified two proteins as potential therapeutic targets and demonstrated that depleting these proteins in vitro severely impacts on tumour cell viability. We will investigate the impact of targeting these proteins in mouse models of human gliomas and dissect the mechanism that leads to ....Glioblastoma Multiforme (GBM) is a high grade brain tumour for which current treatment modalities are inadequate. Tumour recurrence is almost inevitable and average life expectancy is measured in months. We have identified two proteins as potential therapeutic targets and demonstrated that depleting these proteins in vitro severely impacts on tumour cell viability. We will investigate the impact of targeting these proteins in mouse models of human gliomas and dissect the mechanism that leads to their upregulation in tumour cells.Read moreRead less
EphA2 And EphA3 Maintain Tumour Initiating Cells And Are Therapeutic Targets In Brain Cancer
Funder
National Health and Medical Research Council
Funding Amount
$612,860.00
Summary
High-grade glioma (HGG) is the most common adult brain cancer; current treatments have increased survival times by months only. Our studies have shown brain cancer specific expression of a family of cell surface proteins called Eph receptors. Furthermore we have shown targeting these receptors with Eph antibodies leads to a significant reduction in brain cancer tumour growth. We now propose to test targeting these receptors in combination to achieve greater responses with minimal side effects.
The blood-brain barrier is a major impediment to the treatment of brain tumours because it prevents most anti-cancer drugs from entering the brain, and brain tumour, from the bloodstream. This proposal examines new approaches to open the blood-brain barrier to allow the use of existing highly potent anti-cancer drugs as brain cancer therapies. Successful outcomes of this work could lead to substantial improvements in the outcomes for brain tumour patients.
Somatic Retrotransposition Drives Neoplastic Mutagenesis In Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$667,342.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly found to play major roles in biology. In a recent landmark publication in Nature, we demonstrated that retrotransposons move in the healthy human brain. In the current study, we will use cutting-edge technologies to determine whether brain cancer can occur as a result. This will provide new perspectives of the genetic basis for cancer.
Developing Novel Agents To Prevent Tumour Recurrence In Glioblastoma
Funder
National Health and Medical Research Council
Funding Amount
$1,089,561.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called KDM4 (using 'KDM4 inhibitors') improves chemotherapy outcomes with new drugs also discovered in our laboratory. This project will examine a novel drug combination treatment for glioblastoma patients and generate evidence for initiation of clinical trials. This could initiate a novel therapy that could significantly extend patients' lives.