The Role Of Aspirin In The Prevention Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,725,799.00
Summary
ASPREE is a large, phase 3 clinical study of health participants over the age of 70 years who have been randomized to either continuous low dose aspirin or placebo for an average of 5 years. This grant is concerned with collecting long-term follow-up for an additional 5 years, especially for evidence of colorectal cancer (CRC) as well as the exploration of potential mechanisms of action by which aspirin may prevent the development of CRC.
Engineering MYCN Models Of High-grade Serous Ovarian Cancer (HGSC)
Funder
National Health and Medical Research Council
Funding Amount
$797,478.00
Summary
The most lethal type of ovarian cancer, high-grade serous cancer (HGSC), can be divided into four subtypes based on gene patterns. One subtype involves a set of genes/proteins that, in their specific combination, result in activation of a pathway known as MYCN. As most HGSC start in the fallopian tube, we are using fallopian tube material to make new MYCN HGSC models to observe development in the earliest stages. We hope to generate new tests and treatments for this subtype of ovarian cancer.
Exploiting And Defining The Immune Regulatory Activities Of BET Bromodomain Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$923,222.00
Summary
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumor responses. We have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. We will define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumors.
Interplay Between Metabolic Reprogramming And Oncogenic Signalling In The Cellular Response To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$654,035.00
Summary
Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC). We seek to uncover an intimate link between cell metabolism and oncogenic signalling pathways in regulating the cellular response to chemotherapy. Our studies will identify a critical mechanism limiting the therapeutic efficacy of chemotherapy and investigate combination therapy strategies that could improve the treatment of TNBC.
Genomic Profiling For The Prevention Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Bowel cancer is a major health issue but is also a preventable disease. Identifying who has a high risk of developing bowel cancer from someone who has a low risk is an important way to ensure preventative medical treatment is targeted to those who are at the highest risk and will ultimately save lives. I will utilise different genomic profiling approaches to identify risk factors for bowel cancer so that they can be used to identify high risk people in the population.
Role Of MACROD2 Loss In DNA Repair, Chromosomal Instability And Development Of Colorectal Cancer: Clinical And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$772,871.00
Summary
The MACROD2 gene is deleted in one-third of human bowel cancers. We have discovered that MACROD2 deletion causes defective DNA repair and tumour chromosomal instability. Here, we will use novel laboratory models to show that MACROD2 loss actively promotes bowel cancer development. We will test the clinical implication of MACROD2 loss for predicting tumour therapy response and will investigate the potential of exploiting this deficiency for drug targeting.
Unlocking Hidden Cancer Drivers Using Transcriptome Data
Funder
National Health and Medical Research Council
Funding Amount
$700,473.00
Summary
New sequencing technologies allow us to get an unbiased look at the molecular signalling in a tumour. However this information is very complex and need specialised methods in statistic and computation in order to make new discoveries. Here will will develop analysis methods to find novel transcriptional variants in cancer and then test them in the lab in order to understand if our discoveries are responsible for causing cancer.
Regulation Of TNF Expression In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$728,447.00
Summary
By studying a spontaneous mutation in mice, we have found an error in the TNF gene (a major factor in many inflammatory diseases) that causes severe arthritis, heart valve disease and gut inflammation. We have also identified new regulators of TNF expression, which might be useful therapeutic targets to limit inflammation. We intend to study the role of these regulators in controlling the expression of TNF, and the link between chronic inflammation and the development of cancer.
The Role Of CD73 In Cancer: Validating A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
We here propose to investigate the role of a specific immune-suppressive molecule called CD73 in cancer. We will test the therapeutic activity of blocking CD73 with a monoclonal antibody for cancer treatment, either used alone or in combination with immune-activating agents and chemotherapy.
Targeting Bone Marrow Mediated Angiogenesis And Metastasis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,006.00
Summary
Despite advances in treatment and diagnostics breast cancer (BC) remains one of the leading causes of death in women. Metastases and tumour blood vessel recruitment are linked. Work by Dr Mellick and others has shown that host bone marrow contributes endothelial progenitor cells (EPCs) to tumour vasculature. The chemokines and their receptors, which differentiate EPCs from tumour vessels, will be knocked down in the tumour cells and EPC progenitors with the aim of preventing tumour spread.