To reduce mortality and
morbidity and improve the quality of life of men with prostate
cancer by facilitating translational research that will lead to
improved prostate cancer management.
How it came about
Scientific Basis for a National Prostate Tumour BioResource in Australia
The BioResource Management Committee
Working Model for the BioResource
Phase I Activities - Development of the BioResource Web Site
Phase II - Development of a Database of Archived Tissues Available to Other Researchers
Identify and Facilitate Development of Key Infrastructure Required to Enhance Research into Prostate Disease in Australia.
Phase III - Initiation of the Prospective Tissue Collection and the Development of Additional Essential Infrastructure for Prostate Research
Phase IV - Initiate Collaborative Research Proposals
It Came About
The Australian Prostate Cancer Collaboration (APCC) through the Translational Research Working Group determined that in order to enhance translational research endeavours nationally in prostate cancer, there was a need to establish a national prostate tumour BioResource and associated clinical database. The Prostate Cancer Foundation of Australia (PCFA) with the Commonwealth Bank of Australia and Andrology Australia provided the initial funds to establish the BioResource, which the APCC coordinated through a BioResource Management Committee. Our aim is that the BioResource tissue collections will be freely and equitably available to all Australian prostate cancer researchers.
The tissue collections are based at four Australian Capital City nodes and not centralised in one institution. The nodes are in Adelaide (Hanson Institute of Medical Research), Brisbane (Queensland University of Technology), Melbourne (Monash Institute of Medical Research), and Sydney (Garvan Institute of Medical Research). The 4 nodes will be linked via a web-based database, which can be interrogated for assembly of specific tissue cohorts, hence the "virtual face" will allow easy access nationally with the participation of multiple "real" tumour bank nodes Australia-wide.
Scientific Basis for a National Prostate Cancer BioResource
Prostate cancer is the
most common cancer (excluding non-melanoma skin cancers) in older
males and the second most common cause of cancer deaths in males in
Australia and the Western world. The aetiology of prostate cancer is
still unknown. The dilemmas facing clinicians, patients and
asymptomatic older men, with respect to the current choices
available for prostate cancer detection and treatment, have been
expounded in many a scientific and public forum. In spite of the
wealth of published literature regarding the value of PSA testing
and the various treatment options, there have been essentially no
major advances in prostate cancer management in the past decade.
Clearly, we still need more discriminating and specific tests that
can detect localised prostate cancer early and determine the nature
(slow growing or aggressive) of the disease. We also need more
effective therapeutic approaches 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, also a goal of
BioResource Management Committee
the Committee are drawn from the key stakeholders and people with
expertise in tissue bank collections and/or clinical databases
across Australia. This Committee decides the policy and procedures
of the BioResource eg. the nature of the material and data to be
collected, and guidelines for the standardised collection of
tissue/data and for researcher access to the facility.
Teleconferences are held quarterly, and full day workshops are held
annually at the APCC Conference.
Current members of the Management Committee (2009) are:
Judith Clements - (Chairman) Scientist, Queensland University of
Risbridger - Scientist, Monash University, Vic
Robert Sutherland, Scientist, Garvan Institute of Medical
Wayne Tilley - Scientist, Hanson Institute of Medical Research,
David Horsfall – (Project Manager) Scientist, Hanson Institute
Medical Research, SA
Stahl, Pathologist, Adelaide Pathology Partners, SA
Assoc Prof RA
(Frank) Gardiner, Urologist, Royal Brisbane Hospital &
University of Queensland
Dr Kris Rasiah - Medical Oncologist, Garvan Institute of Medical
Taylor - Scientist, Monash Institute of Reproduction &
Williams - Scientist, Monash Institute of Medical Research, Vic
Dr Grant Buchanan - Scientist, Queensland University of Technology, Qld
Bianco-Miotto - Scientist, Hanson Institute of Medical Research,
Broughton - Consumer representative, Qld
Model for the BioResource
Phase I Activities - Development of the BioResource Web Site
The BioResource website
acts as the repository for information about prostate research in
Australia. It will also provide essential information on
prospectively collected and archived prostate tissues available for
Australian research. This has never been done before in Australia.
The main objective of the website is to facilitate and encourage
high quality research, as well as to foster collaboration.
This is being achieved by:
profiling major groups in Australia undertaking prostate (cancer)
research. The information for each group includes a summary of the
key investigators, major prostate-related research grants last 5
years, 20 key prostate-related publications last 5 years, as well as
patents or other outcomes from research undertaken in the field of
prostate disease. Each of the research groups profiled on the
BioResource web site has provided a short overview of their research
activity. This includes a statement of their key areas of research,
identifying areas of expertise and techniques or resources utilised
in their research. The research summary indicates the nature of
experimental systems used in the research program (e.g. human
tissues, experimental models, cell culture systems). Ultimately, non
laboratory-based projects will also be highlighted on the website,
especially those that utilise clinical data sets.
research group profiles showcases Australian prostate cancer
research, and facilitates research collaborations. The profiles are
an important resource for potential BioResource users, and for
future applications to government bodies and other funding agencies
for support of the BioResource.
Until the BioResource prospective tissue and retrospective tissue microarray collections are fully posted on this website (see Phase II below), researchers can obtain information on tissue availability by emailing the Project Manager. The project for which access is required to prostate tissue must be approved by an Institutional Ethics Committee. The procedure is that researchers will approach the Project Manager of the BioResource with details of their project and tissue requirements. If the required materials are not held by the BioResource, the Project Manager will then circulate the enquiry to the research groups participating in the BioResource to determine who might hold the required tissues. The individual institutions would then have the opportunity to initiate collaboration with the applicant. This procedure has to date facilitated initiation of several research collaborations.
The initatives of Phase
I have now been essentially completed.
Phase II - Development of a Database of Archived Tissues Available
A central database with a web portal will be established during the next funding round, and will contain minimum pathology and clinical datasets for both specific sets of retrospective tissue microarrays (TMAs) produced from existing pathology archives (see below) and the prospective frozen tissue collection. Currently, each tissue bank node has a database containing clinical and pathological information associated with the tissues being prospectively collected from prostate cancer patients. Until the central database is available for data mining and cohort building, the prospective tissue collection will be accessed for research via consultation with the Project Manager. Current policy is that 50% only of stored materials from any single patient tissue will be released over the first 5 years, with the remainder being retained until after 5 years of clinical follow up has been collected. When downloaded to the central site, the prospective tissue collection will not be identified in association with any specific institution. Ultimately, researchers who need access to large datasets of a particular tissue type, clinical spectrum or experimental model will be able to interrogate the central database to determine whether suitable tissues are available for their research project. For a synopsis of the tissue currently available, see the BioResource page for further details.
A Tissue Access Policy, specific Letters of Intent (LOI), Full Application Form and procedural guidelines are available. A Letter of Intent and Full Application will need to be submitted to the Project Manager of the BioResource to gain access to both the retrospective TMA sets and the prospective tissue collection. A fee structure is in place to recover some of the costs associated with prospective tissue collection and in production of the microarrays. (See BioResource page for more details)
Identify and Facilitate Development of Key Infrastructure Required
to Enhance Research into Prostate Disease in Australia
The second initiative in phase II has been the development of prostate cancer tissue microarrays (TMAs). Tissue microarrays provide high throughput expression profiling (immunohistochemistry, in situ hybridisation) of candidate genes identified by gene profiling, and facilitate characterisation of protein expression. TMAs can be used to evaluate predictive and prognostic markers, validate candidate diagnostic and therapeutic targets, and aid in the selection of patients with treatments based on expression of target genes. Making TMAs widely available to prostate cancer researchers in Australia will accelerate translational research in prostatic disease and facilitate rapid transfer of molecular discoveries to the clinic.
To facilitate implementation of a human and animal model TMA programme, workshops were held to define the nature of the TMAs required for research purposes and the implementation process. Completed arrays are:
Human disease progression array incorporating normal and cancer
tissues with Gleason grading 4-9, but predominantly 6-7 as per the natural disease spectrum
human pilot array for preliminary testing and reagent optimization
- A normal prostate tissue array with age-related histological change
- Human prostate normal and cancer cell line array
- Development of hormone resistance in murine prostate cancer (TRAMP)
murine pilot array for preliminary testing and reagent optimization
Later TMA sets will incorporate tissues with 5 year follow up of clinical outcome, premalignant histology such as high grade prostatic intraepithelial neoplasia (HGPIN) or advanced stage disease. This microarray program will continue through the next funding period (2010-14).
Access to the completed arrays is now available to researchers, via application to the Project Manager.
Investigators utilising tissue resources from the BioResource will be required to provide the BioResource with the results obtained (e.g. expression of a particular gene/protein). This information will be securely stored in the BioResource database, and will be used for future collaborative research undertaken by the BioResource (see below).
Phase II initiatives are now well under way.
Phase III - Initiation of the Prospective Tissue Collection and the
Development of Additional Essential Infrastructure for Prostate
Phase III began with an identification of the tissue types that were required for the prospective collection, and negotiation with the individual contributing nodes to ensure that there will be a renewable supply of appropriate tissues for the different infrastructure initiatives sponsored by the BioResource. This aspect of Phase III has been completed, and prospective collection implemented at all four nodes, with funding provided by the NHMRC Enabling Grant. Current accrual rate is approximately 55 patients per month.
also involves addressing on an ongoing collaborative basis between
the BioResource Management Committee and the research community, the
precise nature of the infrastructure initiatives that will be
provided to the research community. One option that has created
interest and which would be of immense value to researchers is to
coordinate laser capture micro-dissection of prostate tissues and
extraction of RNA/DNA from the pure cell populations. This would be
performed by a core facility which would undertake to supply the
laser captured micro-dissected cell populations, RNA extracts and
cDNA preparations to investigators. Genomic DNA from peripheral
blood buffy coat leukocytes will also be produced by the BioResource
Phase IV - Initiate Collaborative Research Proposals
Once the core infrastructure requirements have been defined and implemented the BioResource will undertake research activities of its own, such as engaging with national and international genome and proteome consortia, and utilisation of the collective data generated from the use of tissues and TMAs supplied by the BioResource. These meta-analyses will be conducted on a collaborative basis with the researchers who provided the information to the BioResource.