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
Evaluation Of A Novel Antiosteolytic Agent: Potential In Breast-to-bone Metastasis And Mechanism Of Action
Funder
National Health and Medical Research Council
Funding Amount
$352,583.00
Summary
In breast cancer the spread of cancer (metastasis) to bone occurs frequently and causes significant problems including pain, fracture, immobility and paralysis. We have recently discovered that a drug, widely used in Japan and Korea for skin disorders, inhibits breast cancer growth in bone using animal model systems of this disease. This is a very exciting and novel finding. We will further investigate the potential of this drug and identify precisely how it works at the molecular level.
UNDERSTANDING FOCAL ADHESION DYNAMICS IN CELL MIGRATION
Funder
National Health and Medical Research Council
Funding Amount
$268,944.00
Summary
Metastatic (secondary) cancers are a frequent cause of patient mortality. Central to the development of metastasis is cell motility-movement. A key component of cell movement is the way that cells bind and release the extra-cellular matrix as they move. By understanding how the dynamics of cell interaction with the matrix are regulated, we will identify molecules that are critical to the development of metastatic cancer and thus novel targets for inhibition of metastasis.
The spread of cancer to other organs is responsible for 90% of cancer deaths. This proposal seeks to determine how urological tumours (prostate and bladder) spread around the body. Cancer cell and animal models are an integral component of the research, and together with data obtained in human cancer specimens provide a comprehensive, powerful approach to identify key pathways involved in tumour spread. This is critical for the design of new therapies to treat and-or prevent tumour spread.
INVESTIGATIONS INTO THE BIOLOGICAL FUNCTIONING AND PROGNOSTIC VALUE OF NOVEL METASTATIC MARKERS FOR BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$423,564.00
Summary
Breast cancer is the most malignant tumour of women and, despite great advances in detection and treatment, some 30% of women who present with primary breast cancer eventually relapse or die of their disease. Genetic studies have resulted in the rapid identification of the one-third of women at high risk of developing breast cancer because of a family history of the disease: it is hoped that these women will eventually benefit from advances in gene therapy now being developed. For the majority o ....Breast cancer is the most malignant tumour of women and, despite great advances in detection and treatment, some 30% of women who present with primary breast cancer eventually relapse or die of their disease. Genetic studies have resulted in the rapid identification of the one-third of women at high risk of developing breast cancer because of a family history of the disease: it is hoped that these women will eventually benefit from advances in gene therapy now being developed. For the majority of women developing breast cancer, however, the outcome, or prognosis, remains uncertain. The most important indicators of outcome are obtained by study of the excised cancer tissue, and these relate to the speed of growth of the cancer cells and their ability to migrate, or metastasise, to other sites in the body. Studies of cancer tissue using molecular cell biological methods has enabled the identification of several markers that are proving useful as indicators of outcome, and further understanding of the biological functioning of these markers will enable these molecules to be targetted in new treatments aimed at preventing the spread of the cancer. The present study will examine the appearance of new markers for cell migration among breast cancers and measure their value as indicators of outcome. One molecule in particular may be useful as a therapeutic target since it is used by migrating cells during development but is not expressed by normal (non-cancer) adult tissue cells. Towards this, the project will seek to understand how this molecule functions in cell migration.Read moreRead less
Investigating Tumour Development And Metastasis Using A Novel Drosophila Cancer Model.
Funder
National Health and Medical Research Council
Funding Amount
$505,500.00
Summary
The majority of cancers are derived from epithelial cells. The primary cause of cancer related deaths is due to the ability of these epithelial cancer cells to migrate and invade other tissues within the body away from their primary tissue of origin (metastasise). This proposal seeks to understand the pathways that are important in regulating the processes of epithelial cell migration and invasion that are instrumental in promoting the metastatic spread of tumour cells. As controls usually opera ....The majority of cancers are derived from epithelial cells. The primary cause of cancer related deaths is due to the ability of these epithelial cancer cells to migrate and invade other tissues within the body away from their primary tissue of origin (metastasise). This proposal seeks to understand the pathways that are important in regulating the processes of epithelial cell migration and invasion that are instrumental in promoting the metastatic spread of tumour cells. As controls usually operate to induce cell death in any cell that attempts to break away and invade other tissues, this proposal also seeks to understand some of the pathways that are responsible for causing these cells to die. To carry out these investigations we have developed a novel Drosophila model of epithelial cancer development. We use this model because of the ease with which it is possible to carry out complex genetic analyses and so dissect the roles of the many different signalling pathways involved in these processes. The strength of the model is that it is dependent upon genetic alterations that are also implicated in the development and metastatic spread of many mammalian cancers, namely activating mutations in two genes, Ras and Notch. It is expected, therefore, to offer considerable insight into why these activated genes also cause the spread of cancer cells in humans.Read moreRead less
Lymphangiogenesis From Development To Disease: Analysis Of SOX18 Function In The Control Of Lymphatic Remodeling
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Cancers are lethal mainly because they spread (metastasise) to other parts of the body via blood vessels and lymphatic ducts. Pilot studies suggest that suppressing the function of a gene, SOX18, reduces tumour metastasis. We now propose to confirm these findings and study this effect in detail, with the ultimate aim of developing new therapies able to complement already existing anti-cancer treatments.
Targeting Prostate Cancer And Metastases With Novel Anti-tumour Drugs.
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
Prostate cancer is highly aggressive, causing one death every 4 minutes. It is the most common tumour and is the second highest cause of cancer death in men in Western society. Once it escapes the prostate and spreads to other parts of the body it cannot be cured. Current treatment options are limited and cause debilitating side effects. In this study I will investigate a new class of anticancer drugs developed in my host laboratory for prostate cancer treatment.