Molecular Targeting To Telomerase And Cancer Cell Immortality By A Novel Inhibitor
Funder
National Health and Medical Research Council
Funding Amount
$430,812.00
Summary
Infinite growth of cancer cells is a hallmark of cancer. Telomerase is required for cancer cell immortality. Inhibition of telomerase may thus offer an opportunity to stop cancer cells. We have identified an inhibitor of telomerase. This project will study the mechanisms of action of the novel inhibitor, investigating how to control cancer cell immortality as a baseline for more applied anti-cancer therapeutic studies.
Genome-wide Expression Analysis In Advanced Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$326,761.00
Summary
Gastric cancer is the fourth ranked cancer by mortality in Australia. Therapy of gastric cancer is unsatisfactory for two reasons; firstly, how normal stomach cells become cancerous is not well defined. We know long-term infection with the bacteria Helicobacter can lead to these cancers, as can severe acid reflux. The cancers produced by these very different agents look remarkably similar, but must be arising through different pathways. Research to date has not yielded great insight. Secondly, e ....Gastric cancer is the fourth ranked cancer by mortality in Australia. Therapy of gastric cancer is unsatisfactory for two reasons; firstly, how normal stomach cells become cancerous is not well defined. We know long-term infection with the bacteria Helicobacter can lead to these cancers, as can severe acid reflux. The cancers produced by these very different agents look remarkably similar, but must be arising through different pathways. Research to date has not yielded great insight. Secondly, existing therapy, especially chemotherapy, tends to provide a Oone size fits all? solution. Whatever the cause, removal at surgery is the best option for treatment. After this, patients are often treated with chemotherapy. Although improvements in patient comfort have been made, very few patients are cured as a result of this treatment. We need more information with which to match the right patient with the right therapy. We will perform high-throughput analysis of comprehensive arrays of human genes that are affected in gastric cancer. Biopsies from cancerous and normal tissue will be obtained when patients have surgery. This tissue will have the RNA (the Omessage? from each gene) labelled with chemical tags and then applied to DNA Omicrochips?. Each microchip contains about 5000 gene targets; the RNA binds the matching DNA and produces a light reaction. We can read the light output from these 5000 (or more) signals, and perform complex statistical analysis on the results. This will result in several specific Ogene expression profiles? which we will analyse to see which profiles match each situation. Profiles matching reflux-induced cancer and Helicobacter-induced cancer can be compared. This will suggest what unique processes are occurring in the cancer cells. Profiles of patients responding well to therapy may allow the use of Otailor-made? therapy. In the future, insight into cancer pathways should also allow the design of new and more successful therapies.Read moreRead less
The recent cloning of the breast cancer predisposition gene, BRCA1 had an unexpected consequence. Whereas mutations were found in affected individuals from families showing a predisposition to breast and ovarian cancer, mutations were not identified in breast cancers from individuals with no family history. We have identified a type of change called an epigenetic change affecting BRCA1 in breast and ovarian cancers. Epigenetic changes are mechanisms which act at a gene without causing mutations ....The recent cloning of the breast cancer predisposition gene, BRCA1 had an unexpected consequence. Whereas mutations were found in affected individuals from families showing a predisposition to breast and ovarian cancer, mutations were not identified in breast cancers from individuals with no family history. We have identified a type of change called an epigenetic change affecting BRCA1 in breast and ovarian cancers. Epigenetic changes are mechanisms which act at a gene without causing mutations but nevertheless have the stability of genetic change. We plan to examine breast tumours for further epigenetic changes. This project has important implications for our understanding of the development of breast cancer. This new understanding may in turn suggest new strategies for the treatment of breast cancer.Read moreRead less
Histopathological, Magnetic Resonance (MR) And Ultrasound Correlates Of Mammographic Density In BRCA1-2 Mutation Carriers
Funder
National Health and Medical Research Council
Funding Amount
$345,931.00
Summary
Mammographic density (MD), is a major risk factor for breast cancer. The nature of breast tissue underlying MD is not clear. The study will clarify the nature of breast tissue underlying MD as well as determining the breast MRI and ultrasound features that correlate with MD. These findings will enhance knowledge of breast cancer development, and should help to avoid mammography to screen young, high risk women and fulfil a priority objective of Cancer Australia
BIOLOGICAL STUDIES OF A NEW RECURRENT FUSION GENE FOUND IN T-CELL LEUKAEMIA
Funder
National Health and Medical Research Council
Funding Amount
$187,925.00
Summary
Chromosome translocation, in which breaks occur in two chromosomes and rejoin to form two new hybrid chromosomes, is a common genetic alteration in leukaemia. Translocations have been invaluable in identifying genes important in the development of leukaemia. The genetic consequence of translocation is either the deregulation of critical genes adjacent to the breakpoints or the formation of new hybrid genes with novel properties. We have identified the genes at the breakpoints of a T-cell leukaem ....Chromosome translocation, in which breaks occur in two chromosomes and rejoin to form two new hybrid chromosomes, is a common genetic alteration in leukaemia. Translocations have been invaluable in identifying genes important in the development of leukaemia. The genetic consequence of translocation is either the deregulation of critical genes adjacent to the breakpoints or the formation of new hybrid genes with novel properties. We have identified the genes at the breakpoints of a T-cell leukaemia translocation involving chromosomes 4 and 11. The chromosome 11 gene, NUP98, is known to be involved in two other translocations in acute myeloid leukaemia but not in T-cell leukaemia. The chromosome 4 gene RAP1GDS has not been previously shown to be involved in human cancer. This project seeks to understand how the fusion protein NUP98-RAP1GDS (NRG) plays a role in the origin of leukaemia.Read moreRead less
Role Of Cyclin E2 In Hormone-responsive Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$328,194.00
Summary
The female hormone estrogen stimulates the growth of breast cancers by promoting cell reproduction. We have found that cyclin E2, which is part of the machinery that controls cell reproduction, responds to estrogen. Since abnormally high levels of cyclin E2 are linked with earlier relapse in breast cancer, we wish to understand what role it plays in estrogen action and in breast cancer, how its levels are controlled, and whether too much cyclin E2 interferes with drugs that block estrogen action
Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most import ....Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most importantly, we will test our hypothesis that tumours all arose from a single ancestral cancer cell that is transmitted between animals. A cellular transmission has frightening implications for spread of disease, but will allow us to develop appropriate therapeutic strategies to save a unique Australian marsupial from extinction.Read moreRead less
The Assessment Of Clinical And Molecular Adjunctive Tools For The Early Detection Of Oral Mucosal Neoplasia
Funder
National Health and Medical Research Council
Funding Amount
$454,383.00
Summary
It is anticipated that this research will make a significant contribution to our understanding of the natural development of oral cancer and will thus have a direct benefit to patients. The proposed research will enable high quality genetic analysis of individual mutations of relevance to oral cancer via a rapid, reliable, economic, and sensitive screening assay for the assessment of a large number of suspicious oral mucosal lesions.
MMP13 is upregulated in cancer cells and in the tissue that forms around the cancer (stroma). A new MMP13-specific inhibitor reduces breast cancer growth in a mouse model, both at the primary site and also in bone. We will determine the role of MMP13 made by the cancer cells and stroma, respectively, extend the inhibitor work, and identify proteins being cleaved by MMP13. Being a late-stage manifestation, bone metastasis may represent an important clinical trial setting for MMP inhibitors.