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
A Preclinical Model Of Relapse In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$573,515.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease. We also hope to identify markers that can be used to screen for patients at increased risk of relapse.
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.
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
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.
Interaction Of Mc1r With The PRb And P53 Pathways In UVR-induced Melanoma Development
Funder
National Health and Medical Research Council
Funding Amount
$553,479.00
Summary
This project will shed light onto fundamental processes causing UV-induced melanoma (MM). Innate differences between individuals, independent of pigmentation, influence MM development. We will study the mechanisms of UVR-induced MM development in mice carrying gene mutations (Cdk4, Arf, Mc1r) that underpin human MM susceptibility. Knowledge of the sensitivity of an one's MCs to UV could be critical for targeting susceptible groups for health education campaigns and more intense screening.
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.
Genetic Dissection Of The Gp130 Signalling Network; Implications In The Initiation Of Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$447,500.00
Summary
Stomach cancer is a major health problem in the world. It is the second most common cancer and the second leading cause of death from cancer, behind lung cancer. In fact, approximately 10% of all new reported cancer cases world-wide are stomach cancer. The risk of stomach cancer increases with age, with risk rising progressively and peaking at about 60 years of age. Men are affected twice as often as women Like all cancers, stomach cancer results from the progressive acquisition of mutations in ....Stomach cancer is a major health problem in the world. It is the second most common cancer and the second leading cause of death from cancer, behind lung cancer. In fact, approximately 10% of all new reported cancer cases world-wide are stomach cancer. The risk of stomach cancer increases with age, with risk rising progressively and peaking at about 60 years of age. Men are affected twice as often as women Like all cancers, stomach cancer results from the progressive acquisition of mutations in genes that normally ensure a balance between cell growth and cell death. Mutations which predispose individuals to stomach cancer accumulate in the epithelial cells that provide the lining to the stomach. The progression of stomach cancer proceeds through a number of distinct anatomical stages which can be easily recognised by pathologists. Mutations in a number of genes (known as Kirsten-ras, p53) are commonly found in stomach tumours. Moreover, some of the mutations are highly associated with distinct stages of tumour development. As yet, however, we have no real insights into how these mutations cooperate with each other to produce full-blown (malignant) stomach cancer. In our proposal, we are aiming to establish stomach cancer in mice. Our approach will be to use an existing animal model which is predisposed to stomach cancer. We will progressively introduce mutant genes into stomach epithelial cells and study how they cooperate with each other to produce benign, and ultimately, malignant tumours in the stomach of mice. This will help us to understand which mutant genes are required for each stage in tumour development and may provide more rational approaches to stomac cancer screening and treatment.Read moreRead less
Interactions Between Hedgehog And Ras Signaling In Lung Adenocarcinoma
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
Lung cancer is a common and lethal disease in our community. In this project, we explore how signaling pathways that regulate the development of the lung in embryos contribute to the initation and progression of lung cancer. To do this, we use a mouse model of lung cancer in which we can activate embryonic signaling pathways in adult mice to study there effect on the disease. Understanding these pathways will help us to better treat and prevent lung cancer in humans.
Understanding The Development Of Pancreatic Islet Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$579,163.00
Summary
We will use mouse models of pancreatic cancer that we have established previously to investigate the molecular basis of the development and progression of tumours in the insulin-producing cells of the pancreas. We propose to manipulate a small number of candidate genes using established islet cultures and new mouse models in order to characterise the effect they have on islet cell biology and tumorigenesis.