Epithelial - Stromal Interactions In Pancreatic Cancer: Role Of Pancreatic Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$425,750.00
Summary
The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for ....The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for novel approaches to this lethal disease. The proposed project involves an examination of the local tissue reaction around pancreatic cancer. This tissue reaction is usually prominent and the cells involved may determine the extent of local and distant spread of the cancer. Modulation of this tissue reaction may limit pancreatic cancer growth and thus improve outcome.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