Osteosarcoma is the most common cancer of bone. It osurs most frequently in childhood (teenage years) and current therapy is limited to surgery and chemotherapy. We have developed a new model of osteosarcoma that displays a high degree of similarity to human osteosarcoma. We aim to further understand this model and apply these findings to help treat human osteosarcoma.
Cellular And Molecular Determinants Of Preleukaemic And Leukaemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$292,635.00
Summary
It has recently become evident that the formation, growth and relapse of many cancers is driven by a rare population of cancer stem cells (CSCs) that have the unique ability to propagate new tumours and are highly resistant to current therapies. However, which normal cells are transformed into CSCs is not known. We will take a potent cancer gene found in leukaemia, and switch it on and off in specific blood cells in mice to determine which healthy cells can be turned into leukaemic stem cells.
Molecular Mechanisms That Mediate The Anti-osteosarcoma Properties Of Pigment Epithelium-derived Factor (PEDF)
Funder
National Health and Medical Research Council
Funding Amount
$123,453.00
Summary
Cancer results from a sequence of alterations to genes which lead to abnormal cells dividing without control. Osteosarcoma is a cancer involving bone and can rapidly spread to surrounding and distant tissues. A number of mediators have been identified as being able to provide some regulation of this abnormal cell division. Pigment epithelium-derived factor is one such protein and further understanding of how it achieves this could be used for the development of targeted osteosarcoma treatment.
Therapeutic Strategies In Epithelial Cancer Through Signalling Inhibition Of The Epidermal Growth Factor Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$136,250.00
Summary
The growth of cancer cells is regulated by many factors, including the presence of growth receptors on the surface of cancer cells. The epidermal growth factor receptor (EGFR) is present in some normal tissues, but is highly expressed on many common cancers, including brain, breast, lung, head and neck, colon and prostate cancer. We are developing a number of potential therapeutic compounds that act by inhibiting the EGFR in cancer cells. These compounds include a novel monoclonal antibody that ....The growth of cancer cells is regulated by many factors, including the presence of growth receptors on the surface of cancer cells. The epidermal growth factor receptor (EGFR) is present in some normal tissues, but is highly expressed on many common cancers, including brain, breast, lung, head and neck, colon and prostate cancer. We are developing a number of potential therapeutic compounds that act by inhibiting the EGFR in cancer cells. These compounds include a novel monoclonal antibody that binds to EGFR and inhibits its function, and a small molecule that binds to a portion of the EGFR inside cancer cells and also inhibits function. Both of these compounds prevent tumour growth in laboratory studies. This project will examine the mechanisms of action of these compounds, and explore ways to improve their anti-cancer effect. We have also shown that combining these compounds with other therapeutics eg chemotherapy markedly enhances their anti-cancer effect. We will further examine the mechanisms of these effects, and also determine if radiotherapy has additive anti-cancer effects. These studies will provide a basis for improved therapies for cancers overexpressing the EGFR.Read moreRead less
Characterisation And Therapeutic Targeting Of Molecular Pathways That Promote Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$442,573.00
Summary
Breast cancer that has spread to bone cannot be cured. Using the most clinically relevant model of breast cancer available we have identified that tumour cells growing in bone need to suppress immune elimination (by suppressing the Type I interferons) and invade through the bone tissue (by activation of cysteine cathepsins). Studying the functional role of these pathways will provide novel insight into the mechanisms of breast cancer spread to bone that can be augmented therapeutically.
Analysis Of The Apoptotic And Therapeutic Effects Of Histone Deacetylase Inhibitors On Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
Multiple myeloma (MM) is an incurable progressive cancer of plasma cells within blood. It is the second most common blood cancer and represents 2% of all cancer-related deaths. Statistics show increasing incidence and decreasing age of onset. The cause and progression of MM is poorly understood and current treatments are frequently followed by relapse. This project will assess exciting new therapies against the survival of MM cells leading to more effective treatments in the future.
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
The Role Of The TGF-b Superfamily Cytokine MIC-1 In Prostate Cancer Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
We have discovered that a protein called MIC-1 is strongly linked to prostate cancer and is made in large amounts by this tumor. There is a lot of circumstantial evidence that it is involved in the prostate cancer but the proof is missing. We propose to breed mice that are both prostate cancer prone and have genetically modified MIC-1 : mice either are unable to make MIC-1 , or make it in large amounts. We will determine how MIC-1 affects prostate cancer development.
Acute myeloid leukaemia (AML) is a major health problem with only about one third of patients being cured. In addition therapies have changed little over the last 20 years. However there is optimism that with greater knowledge of the biochemical changes in AML that are caused by genetic mutations, more effective treatments will be developed. This project therefore aims to increase understanding of the biochemical interplay between two proteins called c-Cbl and Flt3 that are altered in AML.