The primary goals of the Newcastle ECMC are to increase the interactions between experts from the full range of cancer research and treatment disciplines (surgery, pathology, imaging and adult oncology) so that new cancer treatments are developed in the most informative and expeditious manner to bring benefit to patients. The funding is strategically placed across these various disciplines to enhance ongoing projects and also support new initiatives. The major scientific achievements in the last year reflect both this diversity and the integration being fostered. The major infrastructural achievement in the last year has been the move into the Sir Bobby Robson Cancer Trials Research Centre in the new Northern Centre for Cancer Care on the Freeman Hospital Site and ECMC funded clinical research staff are now housed in this state of the art dedicated early phase trials unit
Advances have been made in pharmacokinetic and pharmacogenomic breast cancer projects, highlighting the integration between ECMC staff supported in the pharmacology laboratory (Professor Boddy) and the early phase clinical trials unit (Professor Plummer), and in the area of urological research where the interaction between the regional clinical team at the Freeman hospital and Professor Robson’s group within NICR is supported by research nursing and laboratory technician ECMC resources. ECMC support of QA management within a laboratory research environment including HTA tissue bank regulatory compliance has allowed significant progress to be made in tissue biobanking, and research outputs from urological and adult solid tumour translational research.

A collaboration with AstraZeneca has led to an MRC Oncology Pilot Industrial Collaboration Award to identify a novel series of small molecule androgen receptor modulators in prostate cancer (MRC contribution £457,234; AZ matched contribution). Professor Craig Robson, the PI on this project, is a key member of the ECMC management team and ECMC staff are located within his research group to facilitate tissue sample collection. Achieving this prestigious funding was facilitated by our strength in translational research and our established/developing prostate cancer tissue microarray bio-banks.

Support for Phase I studies has included the provision of critical PK data in guiding dose-escalation decisions for CRUK-funded studies. These include a Phase I study of Phortress in adult patients and a Phase I study of AT9283 in paediatric patients with solid tumours.

Employment of a clinical research nurse using ECMC funding has enabled the ethical provision of kidney, bladder and prostate tissue accompanied by relevant clinical information to scientists at the Northern Centre for Cancer Research. Rapid transfer of tissue between sites has been facilitated by the ECMC-funded urology technician. The tissue has predominantly been used firstly to define stem-cell like populations and their functional attributes in prostate and bladder and secondly to establish tissue microarrays of renal, bladder and prostate cancer each backed by a clinical dataset.
Much progress has been made in the last 12 months concerning the characterisation of stem-like cell populations in the prostate and urothelium, and the results are currently being written up for publication. In the prostate the work has established differential androgen metabolism pathways involving UDP-glucuronosyltransferases in subpopulations comprising the prostate stem cell model which will be further investigated in prostate cancers. It is possible that subpopulations with dysfunctional androgen metabolism pathways predominate in prostate cancer and, if this is the case, this will give urgently needed and therapeutically useful insights into the development of castration-resistant disease. In the urothelium we have isolated a stem cell population which appears to be more tumorigenic in vivo. We are now beginning to investigate the possible contribution of this cell population to the development of bladder cancer.

We have utilised clinical material collected by our ECMC-funded research nurse and backed by patient, disease, and outcome data. Tissue microarrays of renal, bladder and prostate cancers have been designed and constructed by the urology technician. These are now nearing completion in readiness for rapid evaluation of possible biomarkers and drug-target pathways. We anticipate that this will be a long term resource giving a lasting benefit from the ECMC programme and enabling more rapid decisions regarding the clinical usefulness of laboratory discoveries.

Over the past 12 months over 800 urology tissue specimens from consenting patients have been obtained and used immediately on research studies, or banked either locally or as contribution to national repositories such as PrompT. On the early phase unit over 400 tissue samples (excluding blood derived samples) were collected within study protocols. In addition over 200 further urology patients have consented for their tissue removed for pathological examination to also be used for future research – both these sources are vital for continued population of our tissue microarrays. Retrospective consent and sample collection of more than 100 sarcoma and mesothelioma specimens has also been achieved in the last year.

Additionally with the help of the ECMC funded QA manager considerable progress has been made to establish generic tissue banking from as wide a range of cancer surgical resection specimens as possible, ensuring that necessary ethical permissions and consents are in place to allow access for other researchers for approved projects – with the aim of building a comprehensive library of stored tissue for translational research. Melanoma, osteosarcoma and mesothelioma collections have been set up in the last year, with ongoing prospective collection of skin cancer specimens, this adds to the well established collections in Newcastle of haematological, urological and gynaecological samples. The mesothelioma and osteosarcoma retrospective collections have been used to validate assays for and support the findings of prospective studies of predictive biomarkers for the multi-targeted antifolate pemetrexed in these patient populations, and the results of both these studies are being prepared for publication.