Breast cancer remains the major form of cancer diagnosed in women, and is still the leading cause of cancer death. There remains a pressing need to find better ways to treat this disease. Increasingly, cancer treatments will make use of a growing knowledge of the factors that normally regulate cell growth, and will apply this knowledge to make cancer cells more sensitive to existing anticancer treatments. We are proposing here to study the hormone calcitonin as a novel regulator of cancer cell g ....Breast cancer remains the major form of cancer diagnosed in women, and is still the leading cause of cancer death. There remains a pressing need to find better ways to treat this disease. Increasingly, cancer treatments will make use of a growing knowledge of the factors that normally regulate cell growth, and will apply this knowledge to make cancer cells more sensitive to existing anticancer treatments. We are proposing here to study the hormone calcitonin as a novel regulator of cancer cell growth. Calcitonin is better known as a hormone that inhibits bone loss, by acting on bone resorbing cells called osteoclasts. However, our present proposal is based on our recent finding that the receptor for calcitonin is for some reason also found in many breast cancers. Moreover, we have shown that calcitonin can potently inhibit the growth of cells that have the calcitonin receptor on their surface. We plan to extend these findings in 4 ways: 1 We will make use of a large bank of breast cancer samples at the Royal Adelaide Hospital to determine whether the presence of the calcitonin receptor in breast cancers is related to other features of the tumours, such as their propensity to spread to other organs. 2 We will investigate the mechanisms by which calcitonin slows the growth of cells. 3 We have unique access to new calcitonin-like molecules, called calcitonin mimetics, which we will investigate for the ability to inhibit cell growth. These molecules are much cheaper and probably easier to administer than calcitonin itself. 4 We will investigate whether treatment of cells with calcitonin makes them more sensitive to other anticancer treatments. We hope that success in this project will lead to a more detailed understanding of the way that molecules like calcitonin can regulate cell growth and to new treatment options for cancer.Read moreRead less
A Novel Approach To Restoration Of Tumour Suppression In Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,604.00
Summary
Loss of a tumour suppressor is a key event in every cancer, including lung cancer. Therefore restoration of the expression and/or activity of the tumour suppressor is an attractive approach to anti-cancer treatment. In order to restore tumour suppression, a detailed understanding of the mechanism by which a given tumour suppressor is regulated is required. This application focuses on our discovery of a novel mechanism by which a key tumour suppressor of lung cancer is regulated.
Regulation Of Ribosomal Gene Transcription By C-MYC During Differentiation And Lymphomagenesis.
Funder
National Health and Medical Research Council
Funding Amount
$287,261.00
Summary
A fundamental question in medical biology revolves around how cells respond to the demands to grow and produce proteins, particularly in the setting of the rapid growth of cancer cells. One of the important facets of cellular growth is the production of new proteins needed for all areas of cell life. It is well known that cellular growth involves the production of proteins and this in turn requires the transcription or duplication of ribosomal RNAs (rRNAs). The control of rRNA synthesis, however ....A fundamental question in medical biology revolves around how cells respond to the demands to grow and produce proteins, particularly in the setting of the rapid growth of cancer cells. One of the important facets of cellular growth is the production of new proteins needed for all areas of cell life. It is well known that cellular growth involves the production of proteins and this in turn requires the transcription or duplication of ribosomal RNAs (rRNAs). The control of rRNA synthesis, however, is not well understood. We have identified a novel process to link a cancer causing gene c-MYC to the control of protein production in cells through regulation of rRNA synthesis. Our experiments will examine the hypothesis that c-MYC directly affects the production of rRNA . Finally we will test the link between the ability of c-MYC to cause malignant growth of cells and its role in increasing synthesis of rRNA. These findings may lay the basis for new treatments for disorders of regulated cell growth such as cancer.Read moreRead less
Interactions Between IGFBP-3 And TGFbeta In The Inhibition Of Breast Cancer Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$662,970.00
Summary
A protein first identified by our research group, called insulin-like growth factor binding protein-3 or IGFBP-3, has been shown to be a potent inhibitor of the growth of cancer cells. High levels of IGFBP-3 in the bloodstream are associated with a decreased risk of several cancer types, including breast cancer. However, the way in which this protein prevents cancer cells from growing is poorly understood. This project will investigate an entirely novel idea, developed in our laboratory, that th ....A protein first identified by our research group, called insulin-like growth factor binding protein-3 or IGFBP-3, has been shown to be a potent inhibitor of the growth of cancer cells. High levels of IGFBP-3 in the bloodstream are associated with a decreased risk of several cancer types, including breast cancer. However, the way in which this protein prevents cancer cells from growing is poorly understood. This project will investigate an entirely novel idea, developed in our laboratory, that the actions of IGFBP-3 are intimately connected with the actions of another known cell growth inhibitor called transforming growth factor beta (TGFbeta). We have found that these two proteins initiate the same sequence of events leading to growth inhibition in breast cancer cells, and that a receptor protein required for TGFbeta activity is also needed for IGFBP-3 to be inhibitory. Our work has the potential to explain for the first time exactly how IGFBP-3 stops cancer cells from growing. This is important because it is an abundant protein in the body, and understanding how it acts may lead to the development of new approaches to cancer therapy that exploit our findings.Read moreRead less
Investigating Immune Regulation In The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$288,650.00
Summary
Suppressive factors made by cells of the immune system or cancers themselves and immune regulatory T cells inhibit an effective anti-tumour response. My project aims to investigate the mechanism by which these factors and cells mediate their suppressive function. Understanding these processes in the cancer environment will allow the design of more effective cancer therapies.
The Role Of The M6P-IGF-II Receptor In Regulating Cellular Function
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
We will investigate if a cell surface protein that suppresses the growth of breast cancer cells is also able to reduce the cancer spreading to other organs. The part of the molecule required for this effect will be identified so that smaller forms of the protein can be tested to inhibit tumour spread. Genes and proteins altered by the presence of this protein in breast cancer cells will be examined to determine how the protein suppresses tumours and to identify novel tumour markers.
Immunoregulation, Innate And Adaptive Immunity, Viral Immunology, Ocular Immunology, Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$880,454.00
Summary
The focus on our research is to understand how the immune system responds to viral challenges and how viruses attempt to counteract immune responses. We focus on systemic disease, as well as disease that involve the eye. Understanding how immune responses are regulated will allows us to develop improved therapies
Targeting Immune Suppressive Neutrophils To Improve Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Cancer is the leading cause of death in Australia. Despite the recent successes of cancer immunotherapies, there is an unmet need to overcome primary unresponsiveness and acquired resistance. Today mounting evidence has accumulated that neutrophils contribute to therapy resistance by fostering tumour blood supply and an immune suppressive microenvironment. The central aim of this project is, to improve cancer immunotherapy by blocking an immune suppressive neutrophil response.
Using Mouse Models To Decipher The Function Of Caspase-2 In Limiting Aneuploidy Tolerance And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$871,162.00
Summary
Aneuploidy or abnormal chromosome number is a feature of cancer cells. The extent of aneuploidy is often predictive of prognosis and the effectiveness of cancer treatment. We discovered that a tumour suppressing protein, caspase-2, is important for deleting aneuploid cells that may otherwise become cancerous. In this project we will use cancer models to decipher how caspase-2 safeguards against aneuploidy and cancer to better understand how cancer cells can survive and be targeted for treatment.