Molecular Classification Of Carcinoma Of Unknown Primary
Funder
National Health and Medical Research Council
Funding Amount
$418,250.00
Summary
Carcinoma of unknown primary (CUP) is the fourth largest cause of cancer death. The condition has a particularly poor outlook, with a median survival of less than one year. Current methods for diagnosis of CUP include histopathology and sophisticated imaging. These are successful in approximately 40% of cases. Frequently the reason for the poor outcome in this disease is that the 60% of patients with CUP for whom no diagnosis is made do not benefit from chemotherapy specifically designed for a p ....Carcinoma of unknown primary (CUP) is the fourth largest cause of cancer death. The condition has a particularly poor outlook, with a median survival of less than one year. Current methods for diagnosis of CUP include histopathology and sophisticated imaging. These are successful in approximately 40% of cases. Frequently the reason for the poor outcome in this disease is that the 60% of patients with CUP for whom no diagnosis is made do not benefit from chemotherapy specifically designed for a particular tumour origin. These patients receive a less effective, generic, chemotherapy. The aim of this project is to use microarrays to identify the gene expression profile in many known tumours to create a molecular fingerprint of the various tumour types. By comparing the fingerprint from a CUP with the database we should be able to identify the true tumour type in CUP, and allow patients to benefit from more specific chemotherapy.Read moreRead less
The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
Identifying The Targets Of MiRNA Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$290,600.00
Summary
microRNAs are noncoding RNAs with fundamental functions in biology and significant roles disease. microRNAs control gene expression by destroying RNA or controlling its translation into cellular proteins. To determine how certain microRNAs cause human disease it is essential to know their RNA targets. We are developing methods to identify these targets and aim to apply these methods to identify the targets of microRNAs with known roles in cancer.
Polycomb Group Genes In Murine Lymphomagenesisand Their Impact On Drug Response.
Funder
National Health and Medical Research Council
Funding Amount
$476,815.00
Summary
The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes ....The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes are switched on, where, and when. This determines whether a cell behaves normally or whether it may turn into a cancer cell. When Polycomb Group genes themselves are expressed at the wrong time or place, they can cause cancer. In human lymphoma, these genes have been associated with more aggressive lymphoma. This has also been shown for other cancers such as breast and prostate cancer. In some cases these genes are associated with cancers that do worse following anti-cancer treatment. So far, no research has been published looking the direct impact of the Polycomb Group genes on the success of treatment in a controlled laboratory model. We have used a powerful laboratory mouse model of lymphoma, established in the host laboratory, in which over-expression of the c-myc oncogene in developing B cells causes lymphoma. This model is easy to manipulate and this provides us with a great deal of experimental control, much more than can be achieved from working with patient samples. Two family members, Bmi-1 and Cbx7, cause lymphoma to develop aggressively and we will ask whether two other members, Ezh2 and Rybp do this as well. We will determine whether these 4 genes cause drug resistance in lymphoma, with currently used chemotherapy and also with novel anti-cancer drugs. By increasing our understanding of drug resistance in lymphoma, drugs may be utilised more effectively and new markers identified to predict which drug will be successful in treating a particular lymphoma.Read moreRead less
Evaluation Of A Novel Antiosteolytic Agent: Potential In Breast-to-bone Metastasis And Mechanism Of Action
Funder
National Health and Medical Research Council
Funding Amount
$352,583.00
Summary
In breast cancer the spread of cancer (metastasis) to bone occurs frequently and causes significant problems including pain, fracture, immobility and paralysis. We have recently discovered that a drug, widely used in Japan and Korea for skin disorders, inhibits breast cancer growth in bone using animal model systems of this disease. This is a very exciting and novel finding. We will further investigate the potential of this drug and identify precisely how it works at the molecular level.
Proteomic Screening For Apoptotic Markers In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell li ....The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell lines showed time-dependent decreases in two proteins, identified as S100A6 and ubiquitin. Both are known to be important in cell function. In the proposed project we will build on our preliminary findings to provide important new information central to the understanding of cancer cell biology and apoptosis in addition to evaluating the ability of anti-cancer treatments to induce apoptosis. Using a combination of protein analysis technologies, this project has the potential to provide reliable and novel biomarkers which will indicate the efficacy and selectivity of anti-cancer treatments in inducing tumour cell death. The knowledge gained in this project will aid clinical assessment of the response to cancer treatment(s) in patients in the form of specific screening assays, and may result in identification and development of effective new agents for cancer treatment and prevention. Furthermore, the outcomes of this project will increase our understanding of fundamental cancer cell biology and apoptosis.Read moreRead less
Integrin Beta3 As A Therapeutic Target For Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$431,675.00
Summary
There are limited effective treatments for advanced breast cancer. The project investigates the role of a protein called integrin beta3 in the spread of breast tumours to bone, the most common site of secondary tumour formation (metastasis) in breast cancer patients. We will determine if the presence of integrin beta3 in breast tumours identifies patients at risk of developing bone metastases and test novel drugs against integrin beta3 in mice.
KConFaB - A CONSORTIUM FOR RESEARCH ON FAMILIAL BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$1,624,711.00
Summary
Breast cancer is the most common disease of women. In families with an inherited form of breast cancer, nearly half the women in every generation can develop the disease. The aim of this Australia-wide study is to collect clinical, epidemiological and genetic data on approximately 700 of these severely-affected families. This national resource will be of great value for researchers who want to identify and characterize the genetic and life-style factors that affect the onset and progression of t ....Breast cancer is the most common disease of women. In families with an inherited form of breast cancer, nearly half the women in every generation can develop the disease. The aim of this Australia-wide study is to collect clinical, epidemiological and genetic data on approximately 700 of these severely-affected families. This national resource will be of great value for researchers who want to identify and characterize the genetic and life-style factors that affect the onset and progression of the disease. The data emerging from the study will lead to more accurate genetic counselling, better surveillance and, ultimately, better methods to prevent and treat the disease in families who inherit a predisposition to the disease.Read moreRead less
Characterisation Of A New Family Of Proteins Involved In Cell Signalling, RNA Metabolism And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of th ....We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of these RNA-binding proteins have been identified. We have shown that the novel protein discovered in our laboratory is perturbed in cancer and we are interested in characterising its putative role in cancer. The results established in our laboratory so far would indicate that generally, G3BP-2 is expressed in normal tissue and it expression changes in some cancers studied so far. Considering that G3BP-2 lies in a pathway known to be involved in cancer progression it is important to understand what effects the inappropriate expression of G3BP-2 may have on cancer progression and survival. This project is designed to characterise what signals the cell uses to control these proteins and in turn which genes these may effect. In this way we may be able to determine how external signals may effect tumour progression and on what genes this influence is expressed. It would be hoped that this project would increase our understanding of cancer and potentially lead to new diagnostic reagents and therapies in the treatment of cancer.Read moreRead less
Integrating Wnt-Apc Pathway With TGF-beta Signalling In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$342,364.00
Summary
Colon cancer is one of the leading causes of death of all cancers. Two molecular pathways have been independently implicated in colon cancer development. Emerging evidences suggest that the two pathways may work together in the colon polypus formation. This application will integrate two separate molecular causes to form a new coherent understanding of cancer development and offer new directions in development of novel colon cancer treatment.