Cambridge BRC

Highlights

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Urological Cancer (David Neal)

Funding from the BRC has been used to develop and support the biorepository and to ensure optimum collection of tissue for translational research into prostate cancer. We have recently been undertaking collaborative research with Strangeways in Cambridge and the ICR in London, which has led to important discoveries on novel pre-disposition alleles in prostate cancer.

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Funding from the BRC has been used to develop and support the biorepository and to ensure optimum collection of tissue for translational research into prostate cancer.
We have recently been undertaking collaborative research with Strangeways in Cambridge and the ICR in London, which has led to important discoveries on novel pre-disposition alleles in prostate cancer (Eeles et al., Nat Genetics 2009, Al Olama et al., Nat Genetics 2009, Whitaker et al., Prostate 2010).
The Cambridge component of this research was critically important in defining men with truly low risk disease who were identified during the ProtecT Trial (phase III trial of surgery in prostate cancer).
Reports of other important predisposition alleles are in the process of consideration in Nature Genetics and this collaboration has led to the development of a group which will now take forward in depth DNA sequencing of 500 cases of prostate cancer. The Neal group has carried out the first detailed analysis of how the Androgen Receptor binds to the human genomic using Chromatin Immuno Precipitation (ChIP) and high throughput SOLEXA sequencing, which involved validation of novel targets and genes using the local tissue collections (Massie et al, 2011; EMBO J, in press).

Haematological Malignancies (Tony Green, Brian Huntly, Bertie Gottgens, Alan Warren, Ming Du, Peter Campbell, George Vasilliou)

BRC funding has been used to establish a Translational Research Laboratory (TRL), to undertake sample processing, banking and analysis, and also to appoint a Clinical Senior Lecturer to oversee the TRL which is based in a designated laboratory in the NHSBT building adjacent to research laboratories and to the GMP facility.

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BRC funding has been used to establish a Translational Research Laboratory (TRL), to undertake sample processing, banking and analysis, and also to appoint a Clinical Senior Lecturer to oversee the TRL which is based in a designated laboratory in the NHSBT building adjacent to research laboratories and to the GMP facility.

The TRL team comprises four BRC-funded laboratory staff together with two part-time nurses dedicated to consenting and clinical database management.

The TRL's main role is to process and store a variety of purified cell populations from blood or bone marrow obtained from a wide range of haematological malignancies. It is closely associated with our Regional Haemato-oncology Diagnostic Service which attracts samples from throughout the Eastern Region.

Banked samples support multiple research programs in multiple university departments and neighbouring institutes such as the Sanger Institute and Babraham Institute. Sample banking is most advanced for the myeloproliferative program (1 Nature, 4 NEJM and 2 Lancet papers in the past 5 years) and is currently being extended to include myelodysplasia, myeloma, and acute myeloid leukaemia together with normal haematopoietic stem and progenitor cells.

Samples representing several different cell types have been processed from over 900 patients in the past year. Research highlights over the past year include the unexpected demonstration that JAK2 functions in the nucleus as a histone kinase (Dawson et al Nature 2009), that bone marrow reticulin at diagnosis has important prognostic significance on myeloproliferative tumours (Campbell et al JCO 2009) and that a JAK2 haplotype predisposes to both MPL and JAK2 mutant myeloproliferative neoplasms (Jones et al Blood 2010).

Pancreatic Cancer (Dave Tuveson)

The pancreatic cancer programme has established itself considerably over the past two years, since our clinical team of three medical oncology consultants began to work together for the first time in September 2009. Additionally, with Cambridge BRC and CRUK support we recently hired two research nurses and a data manager.

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The pancreatic cancer programme has established itself considerably over the past two years, since our clinical team of three medical oncology consultants began to work together for the first time in September 2009. Additionally, with Cambridge BRC and CRUK support we recently hired two research nurses and a data manager.

Our pancreatic cancer clinical research team has formulated and successfully opened two investigational trials for pancreatic cancer patients, with each trial springing from our own laboratory-based scientific discoveries.

Our first is a Phase 1-2 clinical trial and involves patients with metastatic pancreatic cancer, where a novel therapeutic strategy using gamma secretase inhibition in combination with gemcitabine will assess our hypothesis that this approach will lead to profound tumour necrosis and a survival advantage for patients. This trial is led by Prof Duncan Jodrell in Cambridge, and we are the first in the world to propose this approach.

Our second trial will determine whether 18-F-deoxyglucose can serve as a tracer to determine early response in patients with advanced pancreatic cancer, since we showed in 2009 (Olive et al, Science June 2009) that pancreatic tumours are poorly perfused. Dr David Tuveson directs this trial, involving 5 sites in the UK.

Finally, Dr Tuveson is directing an additional trial that opened early in

2011, for patients prior to resection of pancreatic tumours. This trial will determine whether Hedgehog inhibitors decrease the tumour stroma and impact upon the tumour vasculature.

To propose these trials, we had to first develop a new method of obtaining tumour biopsies that are sufficient for scientific analysis. Therefore, over the past two years, our team of pathologists, radiologists, surgeons and medical oncologists has modified the processing of small needle biopsies that are obtained during endoscopic ultrasound such that the biopsies are now accurate histological representations of the tumour. Our work has shown that our new approach is diagnostically superior to the aspirates performed routinely, and also is more economical. We are currently writing up this method for submission of a manuscript.

Upper GI (Rebecca Fitzgerald).

There have been 2 highlights over the past year:
(i)Development of a non-endoscopic immunocytology screening test (Cytosponge) for Barrett's oesophagus
(ii) Development of new clinical and molecular prognostic algorithm.

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There have been 2 highlights over the past year:

(i)Development of a non-endoscopic immunocytology screening test (Cytosponge) for Barrett's oesophagus (Patent filed UK and internationally, approved as a medical device by Medical Health Research Agency and trademarked).

We have tested our novel screening device in primary care (BEST trial n=500) which showed that the test was feasible and acceptable to patients with very promising accuracy (90% sensitivity and 94% specificity for the Cytosponge compared with gold standard endoscopy) (Kadri et al BMJ 2010).

(ii) Development of new clinical and molecular prognostic algorithm. The current staging system for oesophageal adenocarcinoma is a blunt tool which takes no account of the molecular features of the primary tumour. We have generated and validated a molecular prognostic signature (Saddi et al PNAS 2010) and uncovered gene of prognostic significance in the stroma (Peters et al Gastroentrology 2010). We are now testing this prospectively to see whether we can predict outcome at diagnosis and ultimately incorporate this into routine clinical practice.

Breast Cancer (Carlos Caldas, Helena Earl, Charlotte Coles)

BRC investment was used to fund part of consultant salaries and to support the breast BRC programme of translational research (prognostic and predictive markers and prognostic tools; breast stem cells; monitoring of tumour responses with functional/molecular imaging; translational neoadjuvant studies; novel radiotherapy protocols).

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BRC investment was used to fund part of consultant salaries and to support the breast BRC programme of translational research (prognostic and predictive markers and prognostic tools; breast stem cells; monitoring of tumour responses with functional/molecular imaging; translational neoadjuvant studies; novel radiotherapy protocols).

The breast programme in the Cambridge BRC has continued to generate translational research (29 publications in 04-2009/03-2010) that is having a direct impact on NHS-patient management by improved approaches to diagnosis, prognosis and therapy.

Clinical Trials and Lung (Tim Eisen)

The Cambridge Cancer Trials Centre is a collaboration between Cambridge University Hospitals NHS Foundation Trust, Cancer Research UK and the University of Cambridge.

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Trials

The Cambridge Cancer Trials Centre is a collaboration between Cambridge University Hospitals NHS Foundation Trust, Cancer Research UK and the University of Cambridge.

Resources from the BRC are used to support the core common elements of the Cambridge Cancer Trials Centre. During the reporting period the CCTC has established a biostatistical capability in collaboration with the Cambridge MRC Biostatistics Hub.

The CCTC biostatisticians have formed close links with the Cambridge University Hospitals Clinical Trials Office. This will serve as an important model for clinical research across the BRC and early phase trials work is now expanding steadily.

Our strategy is to have an early phase programme in each of our focus tumour types. Accordingly, we are now seeking to appoint 2 CRUK-funded academic consultants - one will be in breast cancer therapeutics and one in cancer therapeutics associated with one of our focus tumour types (prostate, ovarian, upper GI, HPB, lung).

Lung

Between them Papworth Hospital and Addenbrooke's Hospital constitute one of the largest thoracic oncology practices in the country with over 500 new incident cases per annum.

Our own research effort aims to reduce the burden of lung cancer by concentrating on the pre-malignant and early stages of the disease, and financial support from the Cambridge BRC has enabled us to construct the team necessary to build this programme.

It has also funded new research sessions in respiratory medicine and research bronchoscopy, radiology and pathology at Papworth Hospital.

Achievements during the year include: selection as one of the 2 pilot sites for the UK Lung Screening study (PI: Eisen, Rintoul), excellent recruitment to studies investigating pre-malignant lung disease (LungSEARCH; PI: Rintoul), NSCLC staging (ASTER; PI: Rintoul) and management of Mesothelioma (MESOVATS; PI: Rintoul), securing funding for therapeutic study of premalignant lung disease (TIDAL; PI: Eisen).