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.
LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS
Funder
National Health and Medical Research Council
Funding Amount
$461,250.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.Read moreRead less
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Mechanistic Basis Of AP-1-regulated Gene Expression During Colorectal Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$597,802.00
Summary
The spread of colorectal cancers in the body poses a major clinical problem for which current treatment options are inadequate. This project aims to unravel how a specific DNA-binding protein regulates the expression of genes involved in the spread of these cancers. The research is expected to provide a better mechanistic understanding of how disease progression occurs and to identify novel strategies to treat aggressive tumours.
How Does Fra-1 Regulate The Invasive Properties Of Tumour Cells?
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Most cancer deaths occur when tumours spread and destroy vital body functions. The invasion of tumour cells into surrounding tissue is a critical step during the spread of cancer. This project aims to unravel the molecular mechanisms that control the ability of tumour cells to invade into surrounding tissue and subsequently spread to other sites in the body. We expect to identify potential targets to better diagnose and treat the spread of cancer.
Improving Sexual Health In Men With Prostate Cancer: Randomised Controlled Trial Of Exercise And Psychosexual Therapies
Funder
National Health and Medical Research Council
Funding Amount
$583,416.00
Summary
Sexual dysfunction is one of the most common and distressing side effects of prostate cancer. Despite being a critical survivorship care issue, there is a clear gap in knowledge surrounding the optimal treatment of sexual dysfunction in men with prostate cancer. This project examines whether exercise aids in the management of sexual dysfunction and explores if an integrated treatment model incorporating pharmacological, exercise and psychosexual therapies maximises improvement in sexual health.
KConFab - The Kathleen Cuningham Foundation Consortium For Research Into Familial Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$2,176,975.00
Summary
Breast cancer is the most common malignant disease of women. In families with an inherited form of breast cancer, nearly half the women in every generation can develop the disease. The aim of this Australasian-wide study is to complete collection of clinical, epidemiological and genetic data on 1,600 of these severely-affected families. The national resource is, and will continue to be, of great value for researchers who want to identify and characterize the genetic and life style factors that a ....Breast cancer is the most common malignant disease of women. In families with an inherited form of breast cancer, nearly half the women in every generation can develop the disease. The aim of this Australasian-wide study is to complete collection of clinical, epidemiological and genetic data on 1,600 of these severely-affected families. The national resource is, and will continue to be, of great value for researchers who want to identify and characterize the genetic and life style factors that affect onset and progression of the disease.Read moreRead less
Expanding Diagnostic Approaches For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$1,269,355.00
Summary
Currently, there are ~1,000 families who have attended Family Cancer Clinics across Australia who have the hallmarks of having Lynch syndrome, a hereditary bowel cancer syndrome, but who have no gene defect identified, i.e. their cancer is unexplained. Clinicians are challenged by these “Lynch-like” patients as their family cancer risk is unknown. Our research has identified new gene defects in Lynch-like patients. Our aim is to optimise clinical testing approaches for Lynch-like patients.
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.