TRF2 Protein And T-loop Replication In Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$398,156.00
Summary
Telomere loss acts as a clock telling cells when to stop proliferating. Cancer cells ignore this clock and grow indefinitely by preventing the normal loss of telomeres. Little is known about one of the methods cancers use to preserve telomeres, called ALT, which is employed by some brain tumours and other cancers. We will determine if the TRF2 protein is involved in controlling ALT. This will lay the basis for future anti-cancer treatments targeted at ALT.
The overall incidence of primary brain tumours in the Western world is 10 per 100,000 people. Unlike many other tumours, these occur in patients of all ages and comprise the second most common tumour type among children and young adults. Most brain tumours remain incurable. We are using our expertise in the field of neural stem cell research to characterise tumour cells responsible for resistance to treatment, with the final goal of identifying new targets for therapeutic intervention.
A Novel Tumour-targeting Nanoliposome Drug Delivery System For The Treatment Of Malignant Gliomas
Funder
National Health and Medical Research Council
Funding Amount
$445,097.00
Summary
Most patients with malignant brain tumours die within a year after diagnosis due to the difficulty in effectively delivering drugs to the tumour cells. We aim to develop a safe and novel drug delivery system to effectively deliver anticancer drugs and novel anticancer agents to brain tumour cells that remain in normal brain after surgery. The success of this project will bring us a step forward in our efforts to significantly improve the survival rate and quality of life of such patients.
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
Development Of Novel EGFR Tyrosine Kinase Inhibitors For The Management Of Glioma, Head And Neck And Other Cancers
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Abnormalities in EGF-EGFR family signalling pathways have been implicated in many human cancers including glioma, squamous cell carcinome of the head and neck, colon, ovary and prostate, and are associated with poor clinical prognosis, non-responsiveness to chemotherapy, and decreased survival. Inhibitors of these pathways would therefore be useful anti-cancer pharmaceuticals. This proposal outlines experiments aimed at understanding the role of the individual EGFR family members in controlling ....Abnormalities in EGF-EGFR family signalling pathways have been implicated in many human cancers including glioma, squamous cell carcinome of the head and neck, colon, ovary and prostate, and are associated with poor clinical prognosis, non-responsiveness to chemotherapy, and decreased survival. Inhibitors of these pathways would therefore be useful anti-cancer pharmaceuticals. This proposal outlines experiments aimed at understanding the role of the individual EGFR family members in controlling a complex signalling network, and the development of novel small molecule inhibitors of these pathways which are specific for individual EGFR family members and which should prove effective in the management of many forms of cancer. Additionally, the potential synergy of these inhibitors in combination therapy with other anti-cancer drugs and reagents which induce cell death will be investigated. These small molecule pharmaceuticals could easily be produced commercially, and taken into clinical trials, in Australia.Read moreRead less
Regulation Of Mitogenic Signalling Via The Gab2 Docking Protein
Funder
National Health and Medical Research Council
Funding Amount
$141,750.00
Summary
Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. F ....Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. Furthermore, we have identified that another protein, termed PKB, can 'switch off' signalling by Gab2, and that deregulated signalling by Gab2 can make cells cancerous. The aim of this project is to characterize how PKB regulates Gab2, and to investigate whether this mechanism is impaired in human cancers, leading to enhanced Gab2 signalling. The research will provide important information regarding how growth factor signals are transmitted inside cells, and may identify a new cancer-causing gene.Read moreRead less
Molecular Imaging Of Brain Tumour Therapeutic Efficacy
Funder
National Health and Medical Research Council
Funding Amount
$412,200.00
Summary
The prognosis for malignant brain tumour patients that do not respond to intial treatment strategies is very poor. The fact that many of these patients patients will not survive longer than 12 months post diagnosis underscores the need to make treatment management decisions in a timely manner. This project seeks to develop and validate non-invasive early molecular imaging biomarkers that can quantify treatment efficacy months before traditional measures of efficacy are valid.
Human brain, pancreatic and head and neck cancers all have a poor prognosis. A gene critically implicated in these cancers is the epidermal growth factor receptor (EGFR), a key target for new therapies. We have identified a microRNA as a key regulator of the EGFR pathway in these tumors. In this project, we will investigate the functional role of this microRNA in these tumors, and determine if it can work synergistically with other new therapies targeting the EGFR pathway to improve outcomes.