Principal Investigator: Prof. William Watson & Prof. John Fitzpatrick
The Prostate Cancer Research Consortium (PCRC) (http://pcrc.tchpc.tcd.ie), was established in 2003, bringing together clinicians, pathologists, scientists, research nurses and allied health care professionals with a common goal of understanding the molecular and cellular basis for prostate cancer development and progression and the stated aim of translating this information to improve detection, prognosis and treatment of this common disease. The PCRC was created under the Dublin Molecular Medicine Centre, now Molecular Medicine Ireland (http://www.dmmc.ie), and was successful in competitive peer review in obtaining a Programme Grant from Irish Cancer Society in 2003. This grant enabled the creation of the PCRC Bioresource, a collection of clinically annotated biospecimens (tumour and normal biopsy tissue, blood, serum, urine, paraffin embedded tissue, nucleic acids) which provides the critical material for the research projects of the programme. This Core Grant was renewed after international peer review in 2007.
Membership of PCRC: Currently, the consortium includes four clinical sites; Mater Misericordiae University Hospital, St James’s Hospital, Adelaide & Meath incorporating the National Children’s Hospital and Beaumont Hospital and four research institutions; UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin; Institute of Molecular Medicine, Trinity College Dublin; RCSI-Education and Research Centre, Royal College of Surgeons in Ireland and National Centre for Sensor Research, Dublin City University.
Focus of Research:
The PCRC has undertaken a focus of research which aims to (i) identify novel cancer biomarkers which will permit early diagnosis of disease, provide critical information for risk stratification and clinical intervention (ii) determine potential targets and new approaches to kill prostate cancer cells. A comprehensive approach, utilising genomic, transcriptomic and proteomic platforms is underway to interrogate the PCRC Bio-resource and identify novel biomarker candidates. This data underpins focussed research projects, in both early detection and disease progression, to better identify individual patient groups who would benefit from specific treatment strategies, while also informing the experimental manipulation of malignant cells, leading to potential novel therapeutic entities and approaches.
The Prostate Cancer Research Consortium Bio-resource:
The Bioresource: The PCRC has established a multi-site or “Federated” prostate cancer bio-resource at its hospital sites following ethical approval by each of the hospital’s ethics committees. Using the federated collection model, agreed standard operating procedures are implemented across the different sites by dedicated research nurses (informed consent, sample collection and initial processing) ensuring uniformity of the resource. Samples are stored at the collection centres using monitored storage facilities as part of the Clinical Research Centres/Research Institutes, developed as part of Molecular Medicine Ireland through the Programme of Research for Third Level Institutions. The Bio-resource currently has 487 tissue samples with corresponding serum, plasma and DNA isolated from blood samples and 269 urine samples. Comprehensive clinical information is also collected for each patient and their samples including full pathology of the initial biopsy and radical prostatectomy, pre and post PSA and subsequent follow up of the patient.
The Bioresource Information and Management System: Central to the federated collection is the Bioresource Information and Management System (BIMS) architecture, which accommodates the collection and tracking of samples and integration of clinical information. The BIMS web based system stores all the de-identified data from the patients and their samples. This allows investigators to identify what samples are available and where they are located, as well as linking the relevant clinical data in a completely confidential way. The Consortium’s BIMS, developed in collaboration with the Trinity Centre for High Performance Computing (TCHPC) (www.tchpc.tcd.ie) and the company SlidePath (www.slidepath.com) is the first database that has been approved and licensed by the Data Protection Commissioner and fully complies with all National and European regulations. The Bio-resource and BIMS are monitored by the Bio-resource Management and Implementation Committee (see Figure) which also reviews access to the resource.
Linkages to International Bioresources: The current resource represents significant numbers of samples for biomarker discovery and first phase validation which would include the establishment and testing of appropriate technologies for further large scale validation. However larger bio-resources are required for the large scale validation of appropriate biomarkers. For this reason, the PCRC has established a number of international collaborations. These include: Prof Helmut Klocker - University of Innsbruck and the Tyrol Prostate Cancer Screening programme (www.urolab-ibk.at), Prof David Horsfall – Australian Prostate Cancer Bio-Resource (www.apccbioresource.org.au), Dr Sudhir Srivastava Early Detection Research Network (EDRN) of the National Cancer Institute (edrn.nci.nih.gov).
The consortium is also part of the International Cancer Biomarker Consortium– www.fhcrc.org/science/international_biomarker/teams established by Professor Lee Hartwell. Currently negotiations are underway with Prof Coleen Nelson Queensland University of Technology, Institute of Health and Biomedical Innovation, Princess Alexandra Hospital, Brisbane, to establish an Australian-Irish Alliance in Prostate Cancer similar to the Australian-Canadian Prostate Cancer Research Alliance (http://www.accessibility.com.au/news/canadaaustralia-prostate-cancer-alliance-launched). In addition, the Consortium has a number of active international research collaborations, including the National Cancer Institute (Dr Karen Woodson, Dr Mike Emmert Buck) and the UC Davis Cancer Centre (Prof Ralph DeVere White).
Principal Investigators: Dr David Murray and Prof. Padraic MacMathuna
Tumour progression beyond the primary site represents the most lethal aspect of cancer. Our team is therefore focussed on identifying and understanding the biological mechanisms that drive the metastatic progression of gastrointestinal cancers. At the CRC we avail of our close connection with gastrointestinal clinics at the hospital site to obtain patient tissue and biomaterials, thereby ensuring our studies are biomedically relevant and truly translational. We have employed a variety of laboratory techniques to scrutinise the molecular biology of these diseases including microarray analysis, cell culture models and real time PCR. For example, using patient tissue we have identified enhanced levels of the NET1 protein in gastric cancer.
NET1 normally controls the motility of healthy cells, however in the tumour setting it NET1 drives tumour cell invasion, a key hallmark of metastatic cells. Our group has shown that if we remove NET1 from cancer cells we inhibit the invasive capacity of these cells. As a potent mediator of the spread of cancer, NET1 is therefore of important clinical and therapeutic significance. Our ongoing efforts into understanding NET1 biology will ultimately inform the development of a therapy targeting NET with the aim of reducing tumour metastasis and therefore cancer mortality. Our studies have led to the publication and presentation of our data in and at international peer-reviewed journals and meetings respectively. We maintain a strong educational aspect to our programme with 5 MD fellows and 5 summer students having completed their research in our lab over the past 3 years.
Principal Investigators: Dr. Amanda McCann & Prof. John Fitzpatrick
Urothelial cell carcinoma of the bladder (UCB), presentations can be stratified into non-invasive PTa and PT1 tumours, or as invasive/metastatic PT2, PT3 and PT4 cancers. PTa and PT1 patients, have an unpredictable disease progression associated with their biology with some patients remaining disease free, while others develop invasive disease with subsequent multiple recurrencies.
Our bladder cancer research initiatives are specifically focused on identifying epithelial mesenchymal transition (EMT) markers predictive of invasive tumours. One of the genes we are primarily interested in is alpha-t-catenin/(CTNNA3), which is down-regulated in EMT, and catenin undergoes not only loss of heterozygosity (LOH) but also altered imprinting, termed gain of imprinting (GOI), data currently being resubmitted to the British Journal of Cancer (BJC).
Principal Investigators; Prof. Michael Keane & Dr Peter Doran
Over a million people die every year due to lung cancer. Lung cancer is the leading cause of cancer death in Ireland and accounts for over 25% of new cancer cases. Our group are currently performing over 200 lung cancer resections annually at St Vincent’s University Hospital. We propose to establish a biorepositery consisting of lung tissue, blood and clinical data from these patients. We envisage this resource to be of utmost value for developing our translational lung cancer research programme thereby allowing us to identify the molecular mechanisms underpinning this deadly disease. By establishing such a bioresource thereby enabling us to perform top class research we will be able to translate our research findings to clinic thereby improving patient outcomes
Lung cancer is a hetrogenous disease that can be broadly sub divided into two groups; small cell lung carcinoma and non-small cell lung carcinoma. We are interested in studying all subtypes and will therefore aim to collect material from patients in both groups. Non-small cell lung carcinomas (NSCLC) include both squamous cell and adeno-carcinomas. Small cell lung carcinomas (SCLC) originate in neuroendocrine cells, are generally more responsive to therapy than NSCLC however they often present late and therefore characterised by high metastatic potential. SCLC incidence correlate closely with heavy smoking habits.
The establishment of a lung cancer biobank at St Vincents university Hospital will enable our group to lead the way for translational lung cancer research in Ireland. It will enable us to answer clinically relevant questions which have to date remained unanswered.
- Can we obtain a better understanding of the molecular evolution of the disease ?
- Can we predict which patients will respond positively to therapy ?
- Can we develop robust biomarkers of lung cancer ?
Furthermore this approach will allow us to evaluate new therapeutic approaches using ex vivo tissue. Material will be collected from lung cancer patients undergoing bronchoscopies and lung resections. Material will be collected and stored securely at our biobank facility at the UCD Clinical Research Centre at St Vincent’s University Hospital.Paravertebral Anaesthesia and Cancer Recurrence
Principal Investigator: Dr. Donal Buggy
A Paravertebral Anaesthesia and Cancer Recurrence multicentre,international, prospective, randomised, controlled clinical study
Dr. Donal Buggy is Principal Investigator and local site director of the international RCT "Effect of regional anaesthesia during primary breast cancer surgery on breast cancer recurrence and metastases," (Registered trial # NCT (US) 00418457). This is a multicentre, international, prospective, randomised, controlled clinical study in which The Mater including the UCD CRC collaborates with the world No.1 most successful research consortium in perioperative medicine, Outcomes Research Consortium, lead by Prof. Daniel Sessler, Cleveland Clinic.
This group has 12 N Engl J Med, Lancet or JAMA publications in the past 12 years, and it represents a considerable achievement for Dr. Buggy and The Mater that this consortium has embraced our ideas and is focused on addressing this intruiging clinical question. Drs. Buggy and Sessler have submitted multiple grant applications based on this trial, and on experimental, translational research investigating potential mechanisms of the effects of anaesthetic drugs and techniques on breast cancer cell function.