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Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
Follow-up Of A Randomised Trial Of Tamoxifen Or Placebo For Breast Cancer Prevention In High Risk Women.
Funder
National Health and Medical Research Council
Funding Amount
$893,483.00
Summary
Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. Tamoxifen, a non-toxic tablet used to control the growth of breast cancer, has safely been taken by more then a million women long term . This project measures tamoxifen's role in preventing breast cancer in high risk women compared to placebo, in a randomised double blind clinical trial. The trial has the potential to benefit many millions of women worldwide. The study, IBIS I (International Bre ....Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. Tamoxifen, a non-toxic tablet used to control the growth of breast cancer, has safely been taken by more then a million women long term . This project measures tamoxifen's role in preventing breast cancer in high risk women compared to placebo, in a randomised double blind clinical trial. The trial has the potential to benefit many millions of women worldwide. The study, IBIS I (International Breast Cancer Intervention Study), is conducted in Australia by the Australian New Zealand Breast Cancer Trials Group (ANZ BCTG), and internationally by Cancer Research UK (CRUK). On the trial women have regular, annual mammography, 6 monthly clinical checks and take a tablet each day called TAMPLAC, which is either tamoxifen or placebo. The accrual phase has been funded by the NHMRC and the target number of women on the trial was reached ahead of schedule - 7154 internationally including 2674 from Australia. By April 2006 all women will have completed the treatment phase. Funding is now being sought, in Australia, for continued follow-up and investigations of additional risk factors (breast density and types of tumors which occur-have occurred on IBIS I). The ANZ BCTG and all the women involved in IBIS I have demonstrated remarkable commitment. It is now vitally important that the essential follow-up is completed to facilitate analysis of the data, including the post-treatment phase, as well as related risk factors and types of tumors which develop. The only other large randomised trial testing tamoxifen (NSABP P-1) ceased and was unblinded in 1998, with an average follow-up of less than 4 years, the trial had to re-commence follow-up to determine longer term tamoxifen effects. The IBIS 1 study remains the only large, blinded trial in the world, and completion of it's follow-up and analysis is of very high international importance.Read moreRead less
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
DETECTION OF OCCULT DISSEMINATED TUMOUR CELLS AND TUMOUR DNA IN EARLY STAGE OPERABLE BREAST CANCER PATIENTS
Funder
National Health and Medical Research Council
Funding Amount
$561,000.00
Summary
Most of the reduction in breast cancer death rate in recent years is due to earlier diagnosis because of mammographic screening. Even among women with very favorable tumours, at least 20% will die of breast cancer. The risk increases to over 50% in less favorable cases of operable early breast cancer. Current practice relies very heavily upon prognostic factors such as lymph node status and tumour size in determining the risk of subsequent failure and the need for therapy. There is a significant ....Most of the reduction in breast cancer death rate in recent years is due to earlier diagnosis because of mammographic screening. Even among women with very favorable tumours, at least 20% will die of breast cancer. The risk increases to over 50% in less favorable cases of operable early breast cancer. Current practice relies very heavily upon prognostic factors such as lymph node status and tumour size in determining the risk of subsequent failure and the need for therapy. There is a significant risk of under treating good prognosis disease patients (20%) and over treating women with intermediate and high risk disease (40%). The first aim of the study is to use novel molecular methodologies to detect breast cancer cells in the blood of patients with early stage breast cancer at diagnosis. The presence of tumour cells will be correlated with the usual prognostic factors used in the management of women with breast cancer. The patients will be followed long-term to clarify the relationship between disseminated tumour cells in the blood and bone marrow and eventual outcome to assess the effectiveness of these new methodologies in patient management. We will also assess new molecular methodologies which will allow us to track very low levels of disease, and thereby monitor the effectiveness of treatment, and allow prediction of impending relapse. Studying the blood of breast cancer patients represents a unique opportunity for determining whether the cancer has spread before surgery and for monitoring of disease after surgical removal of the tumour. This study may prove invaluable in predicting disease free and survival outcomes and provide a more rational approach to the use of chemotherapy in patients with early breast cancer.Read moreRead less