Melanoma is one of Australia s major cancer problems, but we still do not completely understand why certain people are at higher risk than others. This study is focussed on people who have a strong family history of melanoma, and is part of continuing efforts to identify the gene variants that contribute to melanoma risk. Most of the work described takes place as part of national and international collaborations to map and identify these melanoma susceptibility genes and to characterise their ef ....Melanoma is one of Australia s major cancer problems, but we still do not completely understand why certain people are at higher risk than others. This study is focussed on people who have a strong family history of melanoma, and is part of continuing efforts to identify the gene variants that contribute to melanoma risk. Most of the work described takes place as part of national and international collaborations to map and identify these melanoma susceptibility genes and to characterise their effects. Potential benefits from this research will be a better understanding of the place of genetic testing in assessing people s risk of melanoma, particularly if they have relatives with the disease, and way in which skin features like moles should be taken into account in that assessment. In addition, it is likely that better information about the genes altered in melanoma susceptibility and development will point to useful targets for development of novel anti-cancer agents.Read moreRead less
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.
Phosphatidylinositol 3-kinase Mutations Associated With Ovarian, Colon And Breast Tumours
Funder
National Health and Medical Research Council
Funding Amount
$154,000.00
Summary
Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact ....Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact on our society. Unfortunately, though, we still do not understand the basic molecular and-or biochemical abnormalities that initiate and-or drive the development of these cancers. Recent functional and genetic studies in a number of different tumour types (including colon and ovarian) have suggested that members of the phosphatidylinositol 3-kinase (PI3K) enzyme family may be oncogenes (cancer-causing genes). However, strong evidence confirming a causal role for PI3K in human cancer is yet to be reported. Our research proposal outlines a study to address this issue. We have preliminary data demonstrating mutations in at least one member of this enzyme family in a number of tumours. We now propose to undertake a comprehensive analysis of the spectrum, and frequency, of PI3K mutations that occur in colon, breast and ovarian tumours. These studies will allow us to make a definitive assessment of the role of PI3K in the development human cancer. In addition to furthering our understanding of the processes involved in the initiation and progression of human tumours, this project also has the potential to identify new markers for the early detection of cancer and novel targets for new anti-cancer therapies.Read moreRead less
Identification Of Biomarkers Predictive Of Response To Bevacizumab In Patients With Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$32,628.00
Summary
Despite multimodality therapy, the median survival for patients diagnosed with high grade malignant brain tumours is only 12 months. Patient response to therapy is highly variable. Our aim is to develop a “genetic signature” that will predict response to bevacuzimab (an agent targeting blood vessel formation). Identifying patients who will respond to bevacuzimab will save many patients from a toxic and costly therapy, from which they will derive little benefit.
High Resolution Genome-wide Genomic Analysis Of DCIS To Identify Genes Involved In Disease Initiation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$543,370.00
Summary
DCIS is the most common type of noninvasive breast cancer and in some women may progress to malignant disease but little in know about how it develops. We will bring to bear our experience with cutting edge technology and access to extensive clinical resources to the analysis of a large series of pure DCIS with the aim of identifying previously unknown cancer causing genes. This data will lead to the identification of novel breast cancer genes that will assist clinical management.
Genetic And Epigenetic Biomarkers In High Risk Colorectal Cancer: Predicting Risk Of Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
The main aim of this project is to define the prognostic and predictive significance of specific genetic events in patients with high risk (stage III) colorectal cancer. We attempt to explore the differences between primary tumours from patients with and without recurrence at three years. Data from the project will then be used to define a limited set of biomarkers which will aid in clinical decisions regarding the need for adjuvant chemotherapy after surgery for high risk colorectal cancer.
Defining Steps In The Molecular Pathogenesis Of Lung Cancer Using Immortalized Human Bronchial Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$374,344.00
Summary
Lung cancer remains the leading cause of cancer death worldwide and is caused by abnormalities in DNA. This project aims to further our understanding of this disease by altering known cancer-related genes and studying their effect on lung cancer development. This project also aims to identify novel genes in lung cancer as well as tumour expression profiles which can predict response to chemotherapy agents. In summary, this research will identify new gene targets for therapeutic agents.
Gene And Environmental Factors Influencing The Risk And Outcome Of Childhood Neuroblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$91,573.00
Summary
Neuroblastoma is the most common solid tumour of early childhood. The proposed project will identify gene variations as well as birth characteristics and perinatal factors associated with the cause of neuroblastoma. Understanding the genetic causes of the disease can potentially identify genetic targets for treatment and improve diagnosis, while the identification of risk factors can be translated into interventions for prevention of neuroblastoma.
Identification Of Breast And Ovarian Tumour Suppressor Genes On Chromosome 22 By Functional Complementation
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
Cancer is fundamentally a genetic disease that arises when errors (mutations) accumulate in genes involved in regulating how and when cells grow. An important class of gene involved in this process are the tumour suppressors whose primary function is to inhibit cell growth. It is widely believed that significant improvements in the treatment and diagnosis of cancer will only be achievable once we have a detailed understanding of how these genes work. It is likely that dozens of tumour suppressor ....Cancer is fundamentally a genetic disease that arises when errors (mutations) accumulate in genes involved in regulating how and when cells grow. An important class of gene involved in this process are the tumour suppressors whose primary function is to inhibit cell growth. It is widely believed that significant improvements in the treatment and diagnosis of cancer will only be achievable once we have a detailed understanding of how these genes work. It is likely that dozens of tumour suppressor genes exist in the human genome and of these only a small proportion have been identified. The aim of this study is to identify genes on human chromosome 22 that are involved in the development of breast and ovarian cancer. Genetic evidence from many investigators, including data from our own laboratory, has indicated that multiple tumour suppressor genes are present on human chromosome 22 but as yet none have been positively identified. Part of the difficulty in identifying these genes is that cancer cells often have a lot of genetic damage and it is hard to distinguish the important changes from background genetic noise'. To circumvent this problem we are using a functional cloning approach which identifies tumour suppressor genes by their ability to inhibit the growth of cancers cells grown in culture in the laboratory. Genes that are identified in this way will be evaluated for the presence of genetic mutations in real human cancers which will give us a better idea of their true significance in tumour development. In addition to enhancing our understanding of the process tumour development this project may identify new targets for anti-cancer therapies.Read moreRead less
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