New drugs targeting the immune system have dramatically improved the survival of melanoma patients. Nevertheless, 30-40% of patients responding to these new inhibitor will develop drug resistance. This project utilizes patient tumour samples to examine the mechanisms of acquired resistance to immune checkpoint inhibitors. This information will accelerate the identification of novel combination therapies to improve patient outcomes.
Manipulating Oncogene Addiction And Immunity In The Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
Melanoma is a major Australian health problem and a common cause of cancer death in young adults. Treatment of melanoma has been revolutionised in the last few years, but many patients fail to respond to new therapies or rapidly progress on treatment. This proposal examines the mechanisms that drive resistance to therapy and identifies markers predictive of clinical response. This approach will accelerate the development of new strategies and improve patient care by personalising treatment.
RNA Polymerase I: A Novel Target In The Treatment Of MYC Driven Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is dysregulated during cancer leading to the hypothesis that it may be causative in the malignant process. This application will test this hypothesis using novel inhibitors or ribosome biogenesis in a mouse genetic model termed E�-MYC that faithfully that replicates human B-cell lymphoma. These studies will uncover novel mechanisms in malignant transformation and identify new therapeutics in the treatment of human cancer.
A Transcription Factor Network Constraining The Development Of B Cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$617,531.00
Summary
B cell leukemias are relatively common, often aggressive hematopoietic malignancies and their cause is unknown in many cases. We have found that deficiencies in several transcription factors that normally control B cell differentiation cause B cell leukemias at a high frequency. We wish to identify the key pathways that are regulated by these factors and, in normal cells, prevent leukemic transformation. This will help to identify potential targets for therapeutic intervention.
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.