Intraductal Carcinoma Of The Prostate: Indicator Of Aggressive Disease.
Funder
National Health and Medical Research Council
Funding Amount
$884,377.00
Summary
This proposal addresses the need to improve personalised treatment decisions for men with high risk familial prostate cancer as they have a very aggressive disease progression with a very poor clinical outcome. We will perform biological and pre-clinical studies to improve the clinical diagnosis, prognosis and treatment options for men with germline mutations in BRCA2 or BRCA1 genes who develop prostate cancer.
STICs And STONes: A Randomised, Phase II, Double-Blind, Placebo-Controlled Trial Of Aspirin In Chemoprevention Of Ovarian Cancer In Women With BRCA1 And BRCA2 Mutations
Funder
National Health and Medical Research Council
Funding Amount
$653,892.00
Summary
Women with a BRCA1 or BRCA2 gene abnormality are at increased risk of ovary and fallopian tube (O&FT) cancers and often have their O&FTs removed to prevent cancer. Microscopic cancers are often seen at the time of surgery. Some studies suggest that aspirin might reduce O&FT cancer risk. This study will assign women to daily aspirin or placebo for 6-24 months before their preventive O&FT surgery. It will provide a better understanding of how O&FT cancers start and the influence aspirin may have.
Single Cell Genetic Profiling To Reveal Molecular And Cellular Changes In BRCA Preneoplastic Tissue
Funder
National Health and Medical Research Council
Funding Amount
$202,959.00
Summary
The initial molecular and cellular events that lead to breast cancer in women with BRCA1 or BRCA2 mutations are unknown. We will use state-of-the-art genomic tools (Single Cell RNA-seq and whole genome sequencing) to determine how cancer begins in absence of normal BRCA genes. Single cell genomic profiling of stem and daughter cells from pre-cancerous breast tissue will be used to identify early-indicator molecular changes that could be exploited in the clinic.
BRCA-P: An International Randomised Phase III Study Evaluating The RANK Ligand Inhibitor Denosumab For The Prevention Of Breast Cancer In BRCA1 Mutation Carriers
Funder
National Health and Medical Research Council
Funding Amount
$2,589,049.00
Summary
Women with a faulty BRCA1 gene are at high lifetime risk for breast cancer. Identifying a safe and effective prevention therapy is therefore a ‘holy grail’. We have discovered that denosumab, used to treat osteoporosis or breast cancer spread to bone, could be ‘repurposed’ as a prevention drug. BRCA-P is an international randomised controlled study that will determine if denosumab prevents breast cancer. Associated translational research will facilitate swift transfer to the clinic.
Defining The Role Of RNA Editing In Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$628,945.00
Summary
We are seeking to understand how red blood cells are produced. We have identified that a process called RNA editing may be important in the regulating the production of red blood cells.
Reactivities Of CD8 T Cells To Mutated Neo-antigens In Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
Tumours express mutated proteins (called ‘neo-antigens’) which can be targets of powerful killer T cells which can destroy cancer cells. To understand why these cells fail to cure most cancers we will study neo-antigens identified by modern DNA sequencing methods to identify these neo-antigens & the responses to them. Then it will be possible to design trials in individual patients, e.g. personalised vaccines to ‘force’ the immune system to attack cells bearing these neo-antigens.
A Systems Biology Approach To Defining Therapeutic Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$633,112.00
Summary
Breast cancer is a very complex disease affecting large numbers of women. Current treatment strategies are effective at controlling the disease for patients, however many continue to be burdened by their disease as their tumour either does not respond or develops resistance to the treatment. We will use mathematical approaches to analyse large and complex data sets generated from breast cancers to identify new therapeutic targets and improve patient outcomes.
Prediction, Verification, And Clinical Significance Of Splicing Aberrations Associated With BRCA1 And BRCA2 Variants
Funder
National Health and Medical Research Council
Funding Amount
$572,995.00
Summary
There are many families with sequence changes in the breast cancer genes BRCA1 and BRCA2 for which the consequences cannot be easily predicted. It is not possible to offer informative genetic counselling to these women or their at-risk family members. This study aims to refine computer prediction models that are used to predict if sequence changes disrupt the way the gene product is collated in the cell, and what amount of disruption will lead to cancer. This will improve patient management.
A Comprehensive Analysis Of The Role Of The Alcohol Dehydrogenase Gene Cluster In Alcohol-related Disorders And Esophageal Cancer Through Deep Resequencing
Funder
National Health and Medical Research Council
Funding Amount
$605,323.00
Summary
Excessive alcohol consumption remains a major public health concern in Australia where the burden of mental health disorders is dominated by substance-use disorders. Alcohol dehydrogenases (ADHs) are essential in the breakdown of alcohol in the body and we seek to resequence seven ADH genes with the aim to comprehensively catalogue and identify sequence variants that contribute to risk for consuming excessive quantities of alcohol, alcoholism and esophageal squamous cell carcinoma.
Identifying Glaucoma Risk Variants In The Norfolk Island Genetic Isolate
Funder
National Health and Medical Research Council
Funding Amount
$658,447.00
Summary
Primary open angle glaucoma is the most common form of glaucoma. In this project we will focus on the identification of functional genetic variants influencing development of this disorder, using a powerful whole exome sequencing approach in a large multigenerational pedigree from the Norfolk Island population isolate. The identification of genes influencing glaucoma development would provide invaluable clues to aid in defining the pathophysiology of this common disease.