Identification of novel therapeutic targets for selectively eliminating cancer stem cells in paediatric leukaemia. Leukaemia is the most common form of cancer in children, and while the majority of children can be cured, those who relapse face a dire prognosis. It is widely believed that leukemic stem cells are responsible for relapse and this project will aim to unravel their underlying biology and identify new targets for therapeutic approaches to the disease.
mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patien ....mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patients was observed. This project will provide mechanistic details of involvement of mTOR signalling in pathogenesis of the serous ovarian carcinoma, and develop a rationale for targeting mTOR pathway in these patients. Read moreRead less
Linking Breast Development To Bone Metastasis: Role For The Osteogenic Transcription Factor Runx2 During Breast Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$565,145.00
Summary
Bone is the principle metastasis site of breast cancer and represents a major cause of morbidity and mortality. Runx2 is one potential candidate gene mediating breast cancer metastasis. Using mice with altered Runx2 levels and breast cancer models, this study will examine the role of Runx2 in breast cancer bone metastasis. Identification of a single gene that controls both breast and bone would open a new area of breast cancer research and a new gene against which therapies could be developed.
Targeting mitochondria with mitocans to treat cancer: mechanistic aspects. Mitochondria are the power-house of the cell and also the reservoir of proteins causing the demise of cancer cells, therefore suppressing tumour progression. This project proposes a novel way to modify certain compounds, increasing their level in mitochondria in order to maximise their anti-cancer effect.
Roles Of Cascades Of Transforming Growth Factor-beta And Matrix Metalloproteinases In The Impact Of Cancer Stem Cells On The Neoplasm Formation Of Oral Squamous Cell Carcinoma.
Funder
National Health and Medical Research Council
Funding Amount
$81,793.00
Summary
Failure of treatment of oral cancer patients is because the specific cancer cells escape from chemo-radiotherapy. These cells feature self-renew and fast growth, which are called cancer stem cells (CSC). We will test our hypothesis “the genes of TGF-?1 and MMP initiate CSCs” using our cell-mouse models to arrest cancer progression, and verify the impact of CSC on cancer formation. This study is critical to know how to arrest CSC and offer an opportunity to develop a targeted anti-cancer therapy.
Epigenetics describes how genes can be turned off or on without changing the DNA sequence. Epigenetics plays a major role in cancer development. In this proposal we are investigating a novel hypothesis that in cancer a similar mechanism to imprinting USING NON-CODING RNA is triggered and this promotes the suppression of clusters of genes. The results from this proposal will have major implications to our understanding of gene regulation in cancer and will have important therapeutic value for can ....Epigenetics describes how genes can be turned off or on without changing the DNA sequence. Epigenetics plays a major role in cancer development. In this proposal we are investigating a novel hypothesis that in cancer a similar mechanism to imprinting USING NON-CODING RNA is triggered and this promotes the suppression of clusters of genes. The results from this proposal will have major implications to our understanding of gene regulation in cancer and will have important therapeutic value for cancer treatment.Read moreRead less
The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Role Of Chromatid Cohesion In Colon Biology And Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$628,422.00
Summary
Rad21 is a gene, present in many species and essential for accurate chromosome separation and DNA damage repair. Based on its known function in different species, we predict that its� dysfunction fuels cancer progression by promoting genetic instability, which is commonly associated with human cancers. This study will use unique mouse mutant models to investigate the function of this potential cancer-causing gene in colon cancer.