The Contribution Of Host Caveolin-1 To Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$517,992.00
Summary
Mortality in breast cancer rises to 80% in cases where secondary tumors form in other organs. To improve outcome, a better understanding of the processes involved in cancer spread is needed. Normal cells contribute to the growth and spread of a tumour and are a target for therapy. When a protein called caveolin-1 is lost from normal cells in a tumour, the prognosis for the patient is much worse. The aim of this project is to understand how this protein can regulate the spread of breast cancer.
The Role Of Clathrin In The Spindle Assembly Checkpoint And As An Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
Cell division produces two daughter cells. Incorrect localisation and modification of proteins that regulate mitosis cause errors that can lead to cancer. As well as using a unique machinery mitosis uses proteins involved in non-cell cycle pathways. This project investigates the role during mitosis of one such protein: clathrin. We will identify lead clathrin inhibitory compounds, pitstops, that have potential anti-cancer properties, ultimately to be used as a chemotherapy agent.
Characterisation Of The Tumour Suppressor Function Of Caspase-2
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Aberrant cell death (apoptosis) is associated with many diseases including cancer. Apoptosis is mediated by a group of enzymes called caspases. Recently we have discovered that one of these enzymes, caspase-2, acts as a tumour suppressor. We now wish to validate this finding in several preclinical models of cancer and understand precisely how caspase-2 works to safeguard cells against cancer development. These studies will help better understand cancer and ways to treat it.
Alpha-actinin-4 As An Oncogenic Driver And Therapeutic Target In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$401,786.00
Summary
Despite the recent advances in targeted therapy and immunotherapy, curative treatment of metastatic melanoma remains an unmet health problem. In this project, we will potentially demonstrate that a protein called ACTN4 is abnormally expressed at high levels in melanoma cells and plays an important role for melanoma cell survival and resistance to treatment, and thus identify inhibition of ACTN4, either alone or in combination with other drugs, as a novel approach in the treatment of melanoma.
Role Of LncRNA IDH1-AS1 In Regulating C-Myc Driven-glycolysis And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$685,043.00
Summary
It is thought that understanding cancer metabolism will reveal vulnerabilities that can be exploited in the clinic. Indeed, compared to most normal cells, cancer cells utilise different fuels to sustain proliferation and to adapt to their environment. Herein we have discovered a molecular switch that regulates the key metabolic enzyme IDH1 and show this controls tumour growth. Given this switch may be active in 50% of cancers we anticipate our work will have significance to many cancer types.
Role Of Proline-rich Tyrosine Kinase 2 (Pyk2) In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$85,254.00
Summary
Ovarian cancer is one of the most lethal gynaecological cancers in the developed world. Elevated levels of gonadotropin hormones and cell protein Pyk2 have been implicated in ovarian cancer. Our aim is to determine the role of Pyk2 in growth and metastasis of ovarian cancer when stimulated with gonadotropins. In addition, we aim to identify protein changes which occur in ovarian cancer when stimulated by gonadotropins in order to identify new biomarkers for the disease.
The Role Of Natural Protein Inhibitors In Blocking Breast Cancer Invasion
Funder
National Health and Medical Research Council
Funding Amount
$424,139.00
Summary
The mechanisms required for breast cancer cells to spread outside of the ducts and into the surrounding breast tissue are largely unknown. There is increasing evidence that the cell layer surrounding the ducts (myoepithelium) functions to suppress invasion. We aim to test if a protein inhibitor that is expressed in these cells can preventing breast cancer invasion in models of early breast cancer and if its expression can predict those patients that are unlikely to develop invasive cancers.
Targeting Survival Pathways To Overcome The Resistance Of Human Melanoma To Treatment
Funder
National Health and Medical Research Council
Funding Amount
$332,123.00
Summary
Melanoma is a major Australian health problem. This is believed to be due to resistance of melanoma cells to cell death associated with inappropriate activation of survival signalling pathways. My previous studies have provided a number of insights into resistance mechanisms of melanoma cells to apoptosis. I wish to understand more fully the molecular basis of the survival signalling pathways, and to identify new therapeutic targets for overcoming resistance of melanoma to treatment.
Fzd receptors are often upregulated in gastric cancer, and recent studies have shown that targeting these receptors has be effective at reducing cancer cell growth in other cancers including prostate and breast. This project will use cutting edge technology to firstly determine the specific requirement for Fzd receptors during gastric cancer and then determine the therapeutic benefit of using an antibody to target these receptors in mouse models and human gastric cancer cells.
Molecular Characterisation Of Telomere Trimming And Its Role In Cell Proliferative Capacity
Funder
National Health and Medical Research Council
Funding Amount
$403,439.00
Summary
Telomeres are protective structures at the ends of chromosomes. Telomere length is a major determinant of how many times a cell can proliferate. We have recently discovered a rapid telomere shortening process that we have called telomere trimming. We will analyse the molecular details of this process to determine whether it could be used to shorten telomeres and stop cancer cell proliferation, and whether blocking it could increase cell proliferation in patients with short telomere syndromes.