Mission Statement
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 Cancer BioResource
The
BioResource Management Committee
Working
Model for the BioResource - Phase I Activities
Phase II Activities
Phase III Activities
Phase IV Activities
How
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
the APCC.
The
BioResource Management Committee
Members of
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 are:
-
Professor
Judith Clements - (Chairman) Scientist, Queensland University of
Technology, Qld
-
Professor Gail
Risbridger - Scientist, Monash University, Vic
-
Professor
Robert Sutherland, Scientist, Garvan Institute of Medical
Research, NSW
-
Professor
Wayne Tilley - Scientist, Hanson Institute of Medical Research,
SA
-
Assoc Prof
David Horsfall – (Project Manager) Scientist, Hanson Institute
Medical Research, SA
-
Dr Jurgen
Stahl, Pathologist, Adelaide Pathology Partners, SA
-
Assoc Prof RA
(Frank) Gardiner, Urologist, Royal Brisbane Hospital &
University of Queensland
-
Dr Lisa
Horvath - Medical Oncologist, Garvan Institute of Medical
Research, NSW
-
Dr Renea
Taylor - Scientist, Monash Institute of Reproduction &
Development, Vic
-
Dr Elizabeth
Williams - Scientist, Monash Institute of Medical Research, Vic
-
Dr Mary-Anne
Kedda - Scientist, Queensland University of Technology, Qld
-
Dr Tina
Bianco-Miotto - Scientist, Hanson Institute of Medical Research,
SA
-
Mr Spence
Broughton - Consumer representative, Qld
Working
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:
Identifying and
profiling all 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.
Developing such
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 still obtain collaborative access to tissues held by
the research groups profiled in this website. The project for which
they require access to prostate tissue must be approved by an
Institutional Ethics Committee. The procedure is that researchers
will approach the National Project Manager of the BioResource with
details of their project and tissue requirements. The National
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
to
Other Researchers
A web-based
central database will be established during 2007, which 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 Bio-Resource page.
A Tissue
Access Policy, Letter of Intent, Full Application Form and
procedural guidelines are available. The Letter of Intent and Full
Application will need to be submitted to the National 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
Bio-Resource 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 DNA microarrays, 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 4-10
·
A
human pilot array for preliminary testing and reagent optimization
·
Development of hormone resistance in murine prostate cancer (TRAMP)
·
A
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 normal prostate age-related
histological change. In addition, microarrays of human prostate
cancer cell line culture systems are planned for production.
Access to
the completed arrays is now available to researchers, via
application to the Project Manager.
The
individual institutions (nodes) are contributing the materials for
generation of the TMAs. The process of generating the TMAs is being
subcontracted to the Garvan and Hanson Institutes in the first
instance. The BioResource is providing funding to support the
provision of tissues and the generation of TMAs. 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 only for future
collaborative research undertaken by the BioResource (see below).
Phase II
initiatives now are well under way. Sequential release of the TMA
sets indicated above is expected through 2007.
Phase III - Initiation of the Prospective Tissue Collection and the
Development of Additional Essential Infrastructure for Prostate
Research
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 is being implemented at all
four nodes, with funding provided by the NHMRC Enabling Grant.
Current accrual rate at November 2006 is 50 patients per month.
Phase III
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
ultimately.
Phase IV - Initiate Collaborative Research Proposals
Once the
core infrastructure requirements have been defined and implemented
the BioResource could undertake research activities of its own, such
as 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. |