Molecular Characterisation And Diagnosis Of Malignant Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$421,250.00
Summary
Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in ....Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in cases of mesothelioma is not expected until 2010. MM is one of the most aggressive and debilitating tumours known, with a median survival of 7-10 months and a clinical pattern that usually involves substantial pain and dyspnea. Advances in therapy-prevention of mesothelioma will have not only have a major health impact, but potentially an extraordinary economic impact. MM is predicted to cost the Australian economy around $5 billion in compensation over the next 35-40 years. Government, insurance companies and industry will share that cost. The significance of this disease therefore extends beyond its actual incidence. There is growing evidence in many tumour types that the best diagnostics and treatments for cancer will come about as a result of understanding the molecular logic that underpins carcinogenesis, and designing therapies and diagnostics accordingly. We will carry out a project using the most comprehensive microarrays available to profile gene expression in malignant mesothelioma. We will use the expression data we obtain to fulfil three aims. Firstly, we will use patient outcome information to search for genes whose expression is indicative of response to therapy. Secondly, we will search the data to identify candidate secreted molecules which may be useful in the early detection of MM. Finally, we will develop a molecular assay to unequivocally diagnose MM from cells collected from pleural effusions.Read moreRead less
Molecular Profiling Of Breast Tumour Stem/Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$308,824.00
Summary
Breast cancer is the commonest cancer in women in many countries including Australia, the USA and the UK. The incidence of breast cancer has been increasing over the last decade however mortality from breast cancer has declined. Although there is debate as to the exact reasons for this decline in mortality, it is clear that the introduction of the screening program as well as improvements in treatment have played a significant role. Nevertheless, a proportion of patients will have disseminated d ....Breast cancer is the commonest cancer in women in many countries including Australia, the USA and the UK. The incidence of breast cancer has been increasing over the last decade however mortality from breast cancer has declined. Although there is debate as to the exact reasons for this decline in mortality, it is clear that the introduction of the screening program as well as improvements in treatment have played a significant role. Nevertheless, a proportion of patients will have disseminated disease at presentation and may not fully respond to treatment. In addition a number of patients will go on to form apparent recurrence of the primary tumour and- or distant metastases following what appears to be complete clearance of a tumour. In recent years a new concept has been put forward that might account for some of these recurrences. It is thought that the cells in a tumour do not all divide at the same rate. Instead some cells only divide rarely, and then give rise to other cells which divide rapidly and form the bulk of the tumour. Since these 'tumour stem cells' are slow cycling they will be resistant to existing chemotherapy because this affects rapidly dividing cells. These resistant cells may then go on to form another tumour. We intend to study these 'tumour stem cells' using a range of techniques that will show us how they differ from both the rest of the tumour cells and the different types of normal cells in the breast. By identifying molecules that are different in the tumour stem cells we will then have new targets for therapies that are designed to target these chemotherapy-resistant cells. Such therapies could be used in the future in conjunction with existing therapies to achieve a greater eradication of breast tumours.Read moreRead less
Molecular Epidemiology Of Ovarian Cancer: The Australian Ovarian Cancer Study National Clinical Follow-Up Core
Funder
National Health and Medical Research Council
Funding Amount
$883,244.00
Summary
Ovarian cancer is the seventh most common cancer in Australian women and fifth most common cause of cancer death, with approximately 1200 new cases diagnosed and 750 deaths each year. There is an urgent need to better understand the molecular, epidemiological and genetic characteristics of epithelial ovarian cancer and how these influence response to treatment and clinical outcome. Ovarian cancer is a histologically and clinically diverse disease and the variability in clinical outcome in ovaria ....Ovarian cancer is the seventh most common cancer in Australian women and fifth most common cause of cancer death, with approximately 1200 new cases diagnosed and 750 deaths each year. There is an urgent need to better understand the molecular, epidemiological and genetic characteristics of epithelial ovarian cancer and how these influence response to treatment and clinical outcome. Ovarian cancer is a histologically and clinically diverse disease and the variability in clinical outcome in ovarian cancer patients suggests that reliable predictive factors would be of clinical value. However, it is clear that the collection of hundreds of annotated biospecimens is essential if the interaction of genes and environment in the genesis of this disease is to be understood or the molecular features of this disease dissected. Recognizing that this can only be achieved through large-scale collaboration, the Australian Ovarian Cancer Study (AOCS) was established in 2000 by scientists from the Peter MacCallum Cancer Centre, the Queensland Institute for Medical Research, Melbourne University and Westmead Institute for Cancer Research in collaboration with clinicians across Australia. AOCS has recruited 1105 patients to date and this Research Proposal aims to complete the collection of clinical data on all AOCS patients nationally, to validate the use of microarray gene expression profiles to predict clinical outcome and to find genetic variants that may determine clinical outcome in individual patients. The creation of AOCS has provided a unique oportunity to collect one of the finest ovarian cancer biological sample sets in the world. We believe that this internationally significant study will shed light on the basis of response of ovarian cancer to treatment and provide an ongoing resource for research into the causes of ovarian cancer, and studies on the response to treatment.Read moreRead less
Genome-wide SNP Analysis Of Fibroblasts Juxtaposed Or Distant From Epithelial Breast And Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$401,763.00
Summary
In the past it was believed that the driving factor in the process of cancer devlopment was the cancer tissue itself. More recently however, it has become clear that the process is far more complex and that many aspects of human biology can profoundly influence both an individuals presiposition to cancer and the severity of disease. Many laboratories, including our own, have shown that gene mutations frequently occur in cancer tissue but recent studies have suggested that the apparently normal t ....In the past it was believed that the driving factor in the process of cancer devlopment was the cancer tissue itself. More recently however, it has become clear that the process is far more complex and that many aspects of human biology can profoundly influence both an individuals presiposition to cancer and the severity of disease. Many laboratories, including our own, have shown that gene mutations frequently occur in cancer tissue but recent studies have suggested that the apparently normal tissue surrounding the cancer (often referred to stroma) may also contain mutations. This so called 'cancer associated stroma'(CAS) is also thought to harbour genetic mutations and some studies have shown that without these mutations the cancer cannot survive. At present we have only had glimpses of the genetic alterations that may occur in CAS and there is an urgent need to fully understand the interplay between CAS and frankly cancerous tissue. Our laboratory will utilise high density, genome-wide screening technologies to search for novel mutations in CAS from breast and ovarian cancers. A complete understanding of the role stroma plays in cancer development is likely to lead to novel ways of treating and preventing cancer. Consequently, the identification of the full repertoire of stroma-derived cancer promoting genes is emerging as one of the most important areas in cancer research. The identification of these genes could lead to the development of novel diagnostic markers for use in cancer detection, diagnosis and-or prognosis.Read moreRead less