Biological And Clinical Characterisation Of Human Phosphatidylinositide 3-kinase Mutations
Funder
National Health and Medical Research Council
Funding Amount
$33,626.00
Summary
The frequency of PI3K mutations in tumours, suggests that PI3K is one of the most common human oncogenes. Understanding the biological and biochemical significance of these mutations will provide new insights into the biology of human tumourigenesis and further our understanding of the consequence pathways and the progression of human tumours. Such knowledge will help us to identify more effective markers of prognosis, diagnosis, early detection of cancer and design new anti-cancer therapy.
Enhancement Of The Anti-tumour Efficacy Of Ionising Radiation Through Inhibition Of Phosphoinositide 3-kinase
Funder
National Health and Medical Research Council
Funding Amount
$123,503.00
Summary
Radiation treatment alone is given to many cancer patients, however often it does not prevent cancers from recurring. Significant promise is offered by new drugs that target molecules which play a key role in cancer growth, and combining these drugs with radiation treatment may lead to improved patient outcomes. Understanding how these drugs enhance the anti-cancer effects of radiation is critical to selecting the most appropriate patients for treatment with this combination.
Analysis Of CD95L And TRAIL Apoptotic Pathways In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$423,055.00
Summary
Most patients with the brain cancer malignant glioma die within two years of diagnosis, thus innovative approaches to treatment are desperately needed. Mutations which prevent the precancerous cells from responding to suicide (apoptotic) signals can contribute to tumourigenesis. As standard treatment regimes act by inducing this cellular suicide machinery, tumour cells with apoptotic pathway alterations can be resistant to conventional therapies. Malignant gliomas are typically resistant to chem ....Most patients with the brain cancer malignant glioma die within two years of diagnosis, thus innovative approaches to treatment are desperately needed. Mutations which prevent the precancerous cells from responding to suicide (apoptotic) signals can contribute to tumourigenesis. As standard treatment regimes act by inducing this cellular suicide machinery, tumour cells with apoptotic pathway alterations can be resistant to conventional therapies. Malignant gliomas are typically resistant to chemo- and radiotherapy, and therefore may have altered apoptotic pathways. By identifying the components of apoptotic pathways in glioma cells, rational design of either novel drugs, or treatments which will restore-enable susceptibility of the tumour cells to currently available therapies will be feasible. Here we will focus on the suicide pathways triggered by the molecules CD95L and TRAIL. We will characterise the sensitivity of glioma cells to CD95L and TRAIL, chemotherapeutic drugs and irradiation. We will then systematically survey the molecules implicated in CD95L and TRAIL-mediated cell death, based on studies in other cell types, to determine the relevant components of the molecular pathways which lead to apoptosis following CD95L-TRAIL exposure. We will also assess the roles played by known inhibitors, in determining resistance to CD95L and-or TRAIL, and will perform screens for novel inhibitors of these pathways. This study will elucidate the molecules responsible for the CD95L-TRAIL-mediated apoptosis seen in some glioma cells, and the molecules which confer resistance to these treatments in others. We will also learn whether the typical resistance to chemo- and radiotherapy observed in gliomas is mechanistically linked to resistance to CD95 and-or TRAIL resistance. This knowledge will be valuable for the rational design of diagnostic and therapeutic agents for glioma, and potentially for other diseases.Read moreRead less
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
The steroid hormone estrogen plays a critical role in the development of human breast cancer. Anti-estrogen therapy has been believed to be an effective treatment of breast cancer over more than 100 years. However, the anti-estrogen therapy is still restricted mainly because of that estrogen has fundamental physiological actions and a wide range of beneficial effects on bone, brain, cardiovascular and other targeted tissues. Thus, it has become a primary focus of inquiry to understand how estrog ....The steroid hormone estrogen plays a critical role in the development of human breast cancer. Anti-estrogen therapy has been believed to be an effective treatment of breast cancer over more than 100 years. However, the anti-estrogen therapy is still restricted mainly because of that estrogen has fundamental physiological actions and a wide range of beneficial effects on bone, brain, cardiovascular and other targeted tissues. Thus, it has become a primary focus of inquiry to understand how estrogen specifically functions in breast cancer but not in normal tissues. Estrogen serves different functions involving a series of biochemical reactions called signal transduction pathways that can couple estrogen to a specific function, such as cancer formation. We have recently found that a enzyme named sphingosine kinase (SK) activation triggers a novel signal transduction pathway in regulation of cell growth and tumour formation, and that this pathway was activated by estrogen in human breast cancer cells. Thus, we seek to identify how estrogen activate SK and how they contribute to the development of breast cancer. It will ultimately provide a potential target for therapeutic intervention and may yield new compounds that have clinical benefit for anti-breast-cancer.Read moreRead less
Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in ....Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in order to develop more potent drug analogues. Development of these molecules will involve a collaborative and multidisciplinary link with our industry partner and the use of frontier technologies that may lead to improved health and economic outcomes for Australia. Read moreRead less
Identification of genes regulating breast cancer progression and metastasis. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last thirty years, many women still die from relapse of the disease. Our goal is to identify genes involved in the regulation of breast cancer progression and metastasis. This may lead to the discovery of druggable molecules for better targeted therapies for patients.
Role Of A Novel Tks5-Nck Signaling Pathway In Cancer Invasion
Funder
National Health and Medical Research Council
Funding Amount
$560,434.00
Summary
Invasion and metastasis are major causes of death in cancer patients. Our research has uncovered a pathway that increases the invasive potential of tumour cells in vitro. We now aim to determine if the pathway is relevant in invasion and metastasis in clinically relevant models; how a drug targeting the pathway affects invasion and; the extent to which the pathway is active in human tumours. These studies may identify a new molecular target for anti-invasive drugs.