This collaboration of scientists and clinicians from UCD, TCD and their affiliated teaching hospitals was established in 2004 with funding from the Irish Cancer Society.  The group has secured additional funding from Science Foundation Ireland, British Urological Foundation and the Health Research Board, has delivered significant research outputs and has positioned Irish scientists at the forefront of a major international research collaboration.

The Prostate Cancer Research Consortium (PCRC) is a co-ordinated group of researchers and clinicians whose aim is to improve the diagnosis and treatment of prostate cancer. The group has built a bioresource of tissue, serum/plasma, urine and DNA from 600 patients which fuels a series of ongoing discovery and validation research programme.

The Consortium's achievements include:

• The establishment of a prostate cancer biobank, the first biobank in Ireland to be approved and licensed by the Data Protection Commissioners. Over 550 patients have been recruited to the biobank in the last five years. 
• The publication of over 30 articles in international peer-review journals.
• Researchers in the Consortium have received 19 awards and have made a number of significant discoveries.  For example, PCRC researchers have identified a new panel of biomarkers which could be used to help diagnose the prostate earlier.  
• The PCRC has been involved in the training of 33 young dedicated prostate cancer researchers and doctors.
• The development and fostering of key international collaborations with prostate cancer groups in Europe, Australia, Canada and the USA.

Led by Professor Bill Watson, the consortium now includes:

• Mater Misericordiae University Hospital
• St James’s Hospital, Beaumont Hospital
• Adelaide & Meath incorporating the National Children’s Hospital

• UCD Conway Institute 
• Institute of Molecular Medicine, Trinity College Dublin
• Education and Research Centre, Royal College of Surgeons in Ireland
• National Centre for Sensor Research, Dublin City UniversityThis research programme aims to :-

The Consortium's research focus has been on

1. Establishing a prostate cancer tumour bank to support ongoing research and evaluate patient attitudes to tumour banking
2. Applying genomic and proteomic technologies to identify novel biomarkers allowing the early detection and prognosis of prostate cancer cases
3. Correlating these molecular characterisations with disease progression phenotypes
4. Evaluating novel therapies in pre-clinical & potentially Phase I/II studies

Prostate cancer is the most common non-cutaneus solid organ malignancy among men. While early detection allows for curative therapies, advanced disease represents a challenge to treat with no effective treatment options available - leading to the patient’s death within 6-18 months after its development.

Our research examines the mechanisms by which advanced prostate cancer cells develop resistance to the treatments currently available in the clinic, and to identify novel and more effective targets for therapeutic manipulation.

Previous studies have demonstrated that many changes occur in the cancer cells that do not die in response to therapy. Despite this understanding, it is difficult to manipulate these changes and translate our understanding to more effective clinical approaches. Therefore, we  set out to investigate if targeting the upstream factors that regulate them might constitute a more appropriate therapeutic approach.

Using innovative bioinformatics techniques, we have identified markers associated with advanced disease, which we aim to manipulate in order to induce prostate cancer cells’ death. One interesting marker that we have identified is called Serum Response Factor (SRF). We have shown that SRF is increased in patients with advanced prostate cancer and that its manipulation in the laboratory leads to decreased proliferation of cancer cells. Therefore, SRF could be a promising target for the treatment of advanced prostate cancer.

The potential clinical application of this research is the development of new and more effective drugs for the treatment of advanced prostate cancer, which would benefit patients for whom current therapies have failed. This study will advance the field of research through a more effective understanding of resistance mechanisms. The findings will similarly contribute to and open new research strands that aim to discover novel and more effective targets for therapeutic manipulation in advanced prostate cancer.  

The Irish Clinical Oncology Research Group was established in 1996 by a group of cancer consultants with an aim to create more research opportunities for patients by putting a formal structure in place to make Ireland more attractive as a location to international cancer research groups and the pharmaceutical industry.

In 2000 the group expanded its membership to include Northern Ireland. Membership is open to all Medical, Surgical, Radiation Oncologists, as well as Haematologists and Research Specialists (Oncology Research Nurses, Site staff and Translational Scientists).

Today it counts more than 95% of the Islands cancer treating consultants among its membership ensuring that research into cancer develops at a national level across all localities. Since its incorporation ICORG has opened 260 research protocols and this has allowed access to research treatments for more than 7500 Irish cancer patients.

ICORG has also developed strong links with many leading international cancer research groups such as the ECOG, NSABP, TRIO and CRUK and those in industry developing the most promising new cancer treatments. As a result of these positive relationships Irish patients are now being offered cutting edge research options that previously would only have been available in the United States and Europe.

ICORG currently has numerous studies open in the following Disease Areas: Breast, Lung, CNS, Gastrointestinal, Genitourinary, Gynaecology, Haematology/Lymphology, Head & Neck, Melanoma, Paediatric and Translational.

ICORG is a not-for-profit registered charity, partly funded by the Irish Cancer Society and through a Health Research Board (HRB) grant.

Professor Donal Buggy (Mater Misericordiae University Hospital) has instigated international, randomised clinical trials evaluating the effect of anaesthetic technique during primary cancer surgery on recurrence or metastasis.

Ongoing translational work includes evaluating the effect of serum from patients randomised to the clinical trials on cancer cell and normal human immunocyte biology, including proliferation, migration and apoptosis, and on the effect of the putative new anaesthetic gas xenon on biological functions of cancer cells.

Current cancer models fail to replicate the complex interactions between cancer cells and surrounding tissue. To bridge the gap between basic research and clinical applications, more physiological biomimetic 'human' cell-based models need to be created that accurately reflect the structural and cellular complexity of a developing tumour.

Tissue engineering allows the generation of sophisticated, living, biomimetic 3-D cell systems that mimic the microenvironment of human tissues.  Dr Tom Flanagan and his colleagues have employed such models quite successfully as cardiovascular implants and is now turning his focus to in-vitro "tumour-engineering" which has to date been limited primarily to single cancer cell lines. 

The group hopes that a more advanced functional "heterotypic" tumour replicate would incorporate additional cell types, including stromal fibroblasts and endothelial cells. They are interested in investigating the feasibility of producing a 3-D bioengineered human breast tumour model in-vitro that can accurately recapitulate characteristics of in-vivo solid tumour maturation, namely development of tissue hypoxia/necrosis, stromal reaction and angiogenesis.

Dr Nobue Itasaki's group studies the cellular basis of malignancy focusing on the effect of microenvironment. Cancer cells behave differently when cultured on plastic, in collagen matrix, or on feeder cells, exhibiting differences in cytoskeletal arrangement, mobility and in the ability of breaking-down the basal lamina. They employ in vitro approaches by culturing cancer cells in a 3D matrix. Particular focus is put on the effect of Wnt/b-catenin signalling pathway that is responsible for aberrant cell proliferation as well as maintenance of cancer stem cell niche. 

The Centre for Colorectal Disease at St. Vincent’s University Hospital has led significant research into colorectal cancer over many years.

In the area of translational immunology, the group study human dendritic cells and their role in immuno-compromised patient cohorts e.g. colorectal cancer patients or patients with chronic infection such as Hepatitis C virus.

Using an ex-vivo tissue explant model they have demonstrated that the tumour microenvironment in colorectal cancer inhibits the function of dendritic cells. The group has found that the microenvironment of early-stage tumours is as immunosuppressive as later staged tumours and are further dissecting the molecular mechanism underlying this process to determinine if immunity in early stage cancer patients can predict likelihood of disease recurrence.

Furthermore they have recently characterised a novel population of dendritic cells that are enriched in human liver (CD141+CLEC9a+). This dendritic cell subset is particularly effective in driving the expansion of Th17 cells. The group is investigating the importance of these cells at human mucosal sites and their role in autoimmunity/cancer.

Using array technologies, the group are assessing methylation levels at multiple sites across the genome to determine how patterns of methylation relate to the traditional classifications of colorectal cancer. Results are validated using pyrosequencing and immunohistochemistry to facilitate integration of our findings into patient care. They are assessing the significance of mutations in KRAS and BRAF as molecular markers both in the differential diagnosis of familial colorectal cancer (Lynch syndrome) and also as indices of prognosis in sporadic colorectal cancer.