The ADRI’s research is focused on basic, clinical and epidemiological aspects of asbestos-related diseases. New insight will be translated into more effective ways of prevention, better, diagnostic and therapeutic procedures and novel treatment approaches. In the laboratory a variety of molecular and biological techniques are being applied to blood and tissue specimens stored in the ADRI Biobank, and promising new molecules will be quickly tested in clinical trials.
Dr Glen Reid
MicroRNAs are a recently discovered class of small RNAs that have important regulatory roles. They are implicated in the biology of many cancers, including malignant mesothelioma. Using microarrays we have identified a number of miRNAs that are over- or under-represented in primary mesothelioma cell lines and tumours. These include potential tumour suppressor and oncogenic microRNAs. We are currently investigating the role of these microRNAs using mimics and inhibitors.
Dr Yuen Yee Cheng
Previous research has shown that a number of tumour suppressor genes (TSGs) are silenced by DNA methylation in mesothelioma. Our preliminary data have demonstrated the frequent epigenetic silencing of several TSGs in mesothelioma cell lines, and we have found that this is often due to DNA methylation. A better understanding of the epigenetic regulation of potential TSGs in mesothelioma may help us to understand the involvement of different signaling pathways in malignant mesothelioma leading to new therapeutic targets. Identification of these epigenetic changes in the serum of patients may also lead to early detection of malignant mesothelioma.
Dr Glen Reid, Professor Nico van Zandwijk
Treatment of mesothelioma remains difficult because this group of diseases is intrinsically resistant to most of the traditional chemotherapeutic drugs. We have used RNAi to identify genes involved in mesothelioma cell growth and drug resistance. This work has identified genes that are targets in their own right, as well as those which sensitise tumour cells to chemotherapeutic agents. The targets identified fall into two classes: those with available small molecule inhibitors, and those for which siRNA-based intervention is an option.
Dr Glen Reid
As patients with mesothelioma often present with unresectable stage III or IV disease, palliative chemotherapy is often one of the few therapeutic options, but response rates are modest. The limited efficacy of current treatments has led to considerable research interest in new drug development for mesothelioma. Nucleic acid-based therapy is one of these approaches. In conjunction with our molecular characterisation program, we are investigating the ability of RNAi- and antisense-based molecules to inhibit growth of malignant mesothelioma cells. This work focuses on target identification through rational screens as well as the development of siRNAs that can be used in subsequent preclinical studies.
Dr Michaela Kirschner, Dr Glen Reid
Several proteins in blood have been investigated for their ability to assist in making an early diagnosis of mesothelioma but so far these attempts have not been successful. Recently it has been found that microRNAs are present in circulating blood and can be isolated and quantified from plasma or serum. We are currently characterising the microRNAs in plasma from mesothelioma patients with the aim of identifying a novel diagnostic biomarker. Such a marker may also help to make an earlier diagnosis than with the traditional diagnostic biopsy.
Dr Steven Kao
Despite a poor prognosis in general, the survival of individual malignant mesothelioma patients may show significant variation. To support our search for new markers that reflect prognosis we have established a Biobank, with tissue and blood specimen coupled with clinical information. Using this resource we aim to identify novel biomarkers that could improve prognostication and maybe also predict response to therapy to pave the way for better treatment outcomes for Mesothelioma patients. Techniques such as tissue microarrays and proteomics are being used.
Dr Steven Kao, Professor Nico van Zandwijk
Treatment of Mesothelioma ranges from palliative to radical approaches, with chemotherapy now widely used in both settings. Standardising medical care to provide maximal therapeutic benefit will enhance the welfare of patients. The first step is to understand the current practice of diagnosis and treatment so that gaps in the provision of health care can be identified. Within the framework of a Dust Diseases Board (DDB) funded project, we are investigating the pattern of care in Australian malignant mesothelioma patients and whether variation in the care and outcomes of patients in rural and urban areas exist.
Dr Janette Vardy, Dr Steven Kao
One of the important treatment goals in the management of Mesothelioma is to reduce the high symptom burden that accompanies this disease. However, there is a paucity of data on quality of life (QoL) of Mesothelioma patients and the unmet needs for both patients and carers. We aim to investigate the relationship between QoL, systemic symptoms (such as fatigue, anorexia and cachexia) and inflammatory markers. We will also explore the psychological and unmet needs of caregivers and families of patients with Mesothelioma.
Professor Nico van Zandwijk, Ms Victoria Keena and a National Steering Committee chaired by Dr Andrew Penman, CEO of the NSW Cancer Council
In Australia there are no guidelines for diagnosis and treatment of malignant mesothelioma. Diagnostic approaches for malignant mesothelioma may range from simple aspiration of pleural fluid to VAT (video assisted thoracoscopy) with multiple biopsies. Treatment can vary from symptomatic / palliative approaches to combinations of induction chemotherapy followed by radical surgery and postoperative radiotherapy. To provide an evidence-based guideline for the diagnosis and treatment of malignant mesothelioma and to reduce the variability of care in Australia, ADRI has engaged a team of national experts to develop: Evidence-based guidelines for the diagnosis and treatment of malignant mesothelioma.
Clinical practice guidelines constitute systematically developed statements to assist practitioner and patient in choosing the most appropriate health care. It is anticipated that the malignant mesothelioma guidelines will close the gaps between current clinical practice and the best available evidence and there is no doubt that the welfare and benefit of patients will be enhanced by adopting recommendations derived from a systematic review of the medical literature into policy and practice.
The Guidelines for the Diagnosis and Treatment of Malignant Mesothelioma are being developed in line with the National Health & Medical Research Council of Australia and it is anticipated that they will be published in 2012.