HDC Developing Research Programs

Molecular Diagnostics Research

Dr Terry Walsh, Prof Judith Clements, Dr Sarah Kruger, Dr John Bartley, Prof Tony Pettitt, Adjunct Prof Frank Gardiner

Research outline

PSA, a member of the kallikrein family of proteases, is the best available serum marker for prostate cancer but it is not useful for early detection. New approaches are needed. In a novel cross-disciplinary and internationally competitive approach, we have used MALDI-TOF mass spectrometry to analyse the protein profiles in ejaculate (which has secretions from the prostate that may show abnormalities before any protein changes are seen in the blood) from men with and without prostate cancer. Current plans are to validate this finding in a larger group of men on a prospective basis which will require a robust technical paradigm and to identify the cancer-specific proteins.

Major recent funding

Gardiner, Clements, Walsh, Bartley. Aust Urology Foundation Analysis by MALDI-TOF-MS for the presence of tumour-associated proteins in the ejaculate of men with prostate cancer. 2003 $25,000

Gardiner Clements, Hyland, Lavin. Qld Cancer Fund Diagnosis and prediction of the natural history of prostate cancer: use of ejaculate for molecular profiling 2003 $68,000

Gardiner, Walsh, Bartley, Pettitt, Clements Qld Cancer Fund. 2004 - 2005 $140,000

Epidemiology Research

Core staff: Prof Judith Clements, Prof Beth Newman, Dr Mary-Anne Kedda, A/Prof Philip Morris, Dr Angela van Daal, John Lai, Adjunct Prof Frank Gardiner, Adjunct Prof David Nicol

Research outline

To date, there is no known predictive marker for prostate cancer. There have been several studies reporting putative single nucleotide polymorphisms (SNPs) associated with an increased risk for prostate cancer, but none have been conclusively validated in larger case:control or population-based studies. We have an ongoing program to identify SNPs in functional regions of the PSA, kallikrein and growth factor (IGF) gene promoters that are associated with prostate cancer risk. We have found several new potentially informative SNPs but need to determine their potential in a larger case:control study. Together with Prof Newman we are planning to recruit a Queensland-based cohort that would also provide some different gene-environmental perspectives from existing, geographically distinct cohorts. Prof Newman has extensive epidemiological experience and was instrumental in establishing similar cohorts for breast cancer in the USA and has an extensive track record.

Molecular Therapeutics and Structural Biology Research

Dr Jon Harris, Dr Steve Bottle, Henry Simila, Philip Keymer

Research outline

Our current research indicates that the PSA related kallikreins, growth factors and nuclear receptors (retinoid and androgen receptors) involved in prostate cancer provide a pool of potential therapeutic targets. To leverage these important basic research outcomes, we have initiated a structural biology approach that focuses on molecular modeling, bacteriophage display and synthesis of small molecules as potential modulators of targets in prostate cancer. This group has substantial skills in recombinant protein production, small molecule synthesis and molecular modeling of interacting proteins using advanced computational techniques. The logical extension of this initiative is to obtain primary structural data for rational design of therapeutic compounds by using x-ray crystallography.

Major recent funding

Harris Qld Cancer Fund

Harris QUT ATN Small Grant Mapping nuclear receptor coregulator interaction sites. 2003 $13,500

Onyvax Collaboration

Prof Judith Clements, Adjunct Prof David Nicol, Ms Beth Morrison, Ms Elizabeth McClellan

Description

A major collaboration has been established with Onyvax Ltd, a UK company that has a major interest in development of new, clinically relevant primary tumour cell lines. The QUT /Princess Alexandra Hospital group has been chosen to work with Onyvax to achieve these aims. This is an exciting new opportunity for our combined research teams to be involved in the generation of some of the first new cell lines for prostate cancer and other urological cancers that have been available for decades. The significance of our approach is that these new cell lines, which we will grow from individual tumours from men with prostate cancer, will be more representative of the different types of prostate cancer that each individual man may have. Ultimately, we will have a bank of these cell lines which will cover the spectrum of cancer types and which will not only be enormously useful and more applicable in our studies in the laboratory to identify the genes involved in tumour growth and spread but also be used clinically to treat these cancers via a generalised vaccine approach by our Industry partner, Onyvax.

Major recent funding

Clements, Nicol. Onyvax Ltd (UK) Cell based vaccine therapies. 2003 $410,000; 2004 $400,000

Australian Prostate Cancer Bioresource (Tissue Bank)

Ms Kay Cambourn, Prof Judith Clements

The Australian Prostate Cancer Bio-Resource (Tissue Bank) has been established by a consortium of prostate cancer researchers and clinicians under the auspices of the Australian Prostate Cancer Collaboration (APCC), with significant initial funding from the Commonwealth Bank, Andrology Australia and the Prostate Cancer Foundation of Australia (PCFA). It is co-ordinated from QUT. The Bio-Resource and its associated clinical database are being established in order to enhance the ability of Australian researchers to carry out translational research in prostate cancer. The aim is that the Bio-Resource will be available widely and equitably to all participating researchers and not centralised in one institution and hence will have a "virtual face" that allows the database to be accessed nationally with the participation of multiple "real" tumour bank nodes Australia-wide. In spite of the wide use of PSA testing and the various treatment options available, there have been essentially no major advances in prostate cancer management in the past decade. Clearly, there is a need for more discriminating and specific tests that can detect localised prostate cancer early and determine the nature (indolent or aggressive) of the disease. More effective therapeutic approaches are also needed that are tailored to the disease type and stage, are less invasive and without the current associated high morbidity. These outcomes are the target of the current move worldwide to translational research and the need for a more intimate collaboration between basic and clinical researchers.

Major recent funding

Part of the APCC national consortium - Commonwealth Bank, Andrology Australia, Prostate Cancer Foundation of Australia. 2002-2004 $ 549,000