Manchester Cancer Research Centre. Progress Report November 2011

Transcription

1 Manchester Cancer Research Centre Progress Report November 2011

2 Investing in Infrastructure, Investing in People continued growth and success are of immense importance and benefit to the partnership. Manchester Cancer Research Centre Notable achievements delivered over the past year are highlighted in this report which demonstrates the success of the partnership strategy at the heart of the MCRC. Collaboration both within MCRC partner organisations and the wider cancer research community continues to drive our research strategy and aims to ensure optimal use of resource and strategic integration of research programmes. The progress we have made in achieving research imperatives across the diverse range of disciplines that comprise the MCRC are featured in this report. Looking ahead, we need to accelerate progression and capitalise on the strong partnership that has been forged here in Manchester. This will involve increased investment in infrastructure and people. This year saw the appointment of a new Director at the Paterson Institute for Cancer Research as I stepped down to become Cancer Research UK s Chief Scientist, a role I will undertake along with leading the MCRC and my own research group at the Paterson Institute. It has been a privilege to lead the Institute and the experiences and support I gained during my term as Director will be invaluable as I face the challenges of my new role. The new Paterson Director, Professor Richard Marais, is a leading force in melanoma research and will bring a fresh perspective and enthusiasm as he drives the Institute s research to achieve its potential. The Paterson Institute is very much at the heart of the MCRC so its Professor Ian Jacobs is the new Vice- President and Dean for the Faculty of Medical and Human Sciences within The University of Manchester and brings immense leadership experience, which will be invaluable in strengthening the Faculty over the next few years. Cancer research is a major theme within the University and we look forward to substantial investment in facilities and staff over the next five years. An allied investment in infrastructure is also critical and the new early phase Clinical Trials Unit at The Christie, which is up and running and functioning well, is now optimally positioned to attract clinical academics who will drive increased activity and progress in these essential first trials. Plans for the new landmark MCRC research building are also progressing well with key decisions agreed and the planning submission process on track. With the investments taking place in infrastructure and leadership, we are confident that the MCRC will continue to grow from strength to strength, becoming a focus for world class cancer research and attracting additional resource and research leaders. Professor Nic Jones Director

3 Fifth Birthday Celebration for the MCRC The Manchester Cancer Research Centre hosted an event on Wednesday 2 February 2011 to celebrate its five year anniversary. Key people from the founding partner organisations attended, along with approximately 75 fundraisers from Cancer Research UK, Breakthrough Breast Cancer and The Christie. The event was a great success and attendees enjoyed hearing about advancements that had been made over the last five and plans for the future. The evening event was opened by Dr Mike Oglesby, Chairman of the MCRC Steering Board, and brief talks were given by Harpal Kumar, Chief Executive of Cancer Research UK, Professor Dame Nancy Rothwell, President and Vice- Chancellor of The University of Manchester and Caroline Shaw, Chief Executive of The Christie NHS Foundation Trust. Professor Nic Jones then provided an overview of the success and future plans of the MCRC. He highlighted how advancements had been made in breast and lung cancer, radiation related research, biobanking and imaging. This had been achieved through strategic planning and the development of the research infrastructure in Manchester - the recruitment of new researchers and improvement of facilities. Nic also explained how the partnership was already helping to benefit cancer patients, particularly with the development of new facilities like the new Patient Treatment Centre at The Christie and the Drug Discovery Unit at the Paterson Institute, and how plans for a new dedicated and forward looking research facility for the MCRC were well underway. He concluded by sharing his vision for the future of the MCRC; to be established and recognised as one of the leading comprehensive cancer centres in Europe; to be recognised as a centre of excellence in a number of key cancer research areas; and to bring personalised medicine to Manchester. 3

4 Leading Researchers Join the MCRC Professor Richard Marais, a world leading expert on the underlying causes of melanoma, is to become the next Director of the Paterson Institute for Cancer Research. He takes over from Professor Nic Jones who continues to lead the MCRC and was appointed Cancer Research UK s Chief Scientist earlier this year. Richard is currently Professor of Molecular Oncology at the Institute of Cancer Research in London where he conducts research aimed at understanding the signalling pathways that drive melanoma development and targeting these pathways for therapeutic intervention. He is also Secretary General of the European Association for Cancer Research and has served on many funding and steering committees, including the main science funding committee of Cancer Research UK. The Paterson Institute is home to 16 research groups and, as the Institute is part of The University of Manchester, Professor Marais will also be a full professor of the University. Between now and his official start date in February 2012, Richard will make frequent visits to the Institute to familiarise himself with its operations and its research activities. We are all delighted by this appointment which will continue to strengthen the high quality research at the Institute and I am sure that the future of the Institute will be in good hands, said Professor Jones. Dr Ged Brady has taken up a new position as Senior Translational Scientist in the Clinical and Experimental Pharmacology (CEP) Group at the Paterson Institute, which is led by Professor Caroline Dive. Ged has spent over 30 years developing advanced molecular biological methods and using them to further the understanding of a variety of key biological areas including DNA replication control, cancer initiation and stem cell regulation. He has carried out research in the Max Planck Institute for Molecular Biology (Berlin), the German Cancer Research Centre (Heidelberg), the European Molecular Biology Laboratory (Heidelberg), the Ontario Cancer Institute (Toronto) and has held positions of Lecturer and AstraZeneca Special Fellow at The University of Manchester. Ged joins the Institute from Epistem - a Paterson Institute spin off company that focused on epithelial stem cell work mainly for pharmaceutical companies - where he was Research Director. While at Epistem, Ged was responsible for setting up research and developing the underlying science for Epistem's Novel Therapies and Biomarker divisions. He has more than two decades of experience in fractionating and analysing single cells and has developed a simple kit which can be used for the comprehensive analysis of gene expression in small samples of tissue and individual cells. In his new post, Ged will act as CEP deputy and have responsibility for broadening the biomarker research portfolio, working closely with clinicians and basic researchers to develop assays and biomarkers that can guide treatment in the clinic. While continuing to maintain collaborative links with Epistem, he will be working with the CEP group to continue and develop their internationally recognised excellence in biomarker development and delivery. He will have a key role in increasing the capacity for linking translational research with early phase clinical trials. 4

5 Professor Ian Jacobs took up the post of Vice-President and Dean for the Faculty of Medical and Human Sciences within The University of Manchester in March The role includes responsibility for the Faculty s Schools of Dentistry, Pharmacy, Nursing and Psychology as well as the 5 Schools of Medicine, including Cancer and Enabling Sciences. This breadth of expertise across health science disciplines is a unique aspect of The University of Manchester and provides many opportunities for multidisciplinary interaction and collaboration, not only in cancer research but across the Faculty, University and NHS partners which the new Dean aims to encourage and develop. Alongside his role as Dean, Ian is also Director of the Manchester Academic Health Science Centre (MAHSC) - a federation of seven partners bringing together The University of Manchester and the six research active NHS Trusts in Greater Manchester. With only five AHSCs in England, the remainder of which are located in the south of the country, MAHSC plays a key role in optimising the integration and alignment of academic and NHS activity within the region. Since taking up his post Ian has initiated a strategic review involving all staff in the Faculty, which has led to a proposal for a new matrix structure involving the Schools of Medicine, Dentistry, Nursing, Pharmacy and Psychology and a series of new Faculty Research Institutes. Six Research Institutes are proposed focusing around existing or emerging areas of strength and strategic importance. One will be a Cancer Institute and the others focused on Population Health, Cardiovascular disease, Human Development, Inflammation/Repair and Brain/Behaviour. A major recruitment and investment effort is planned alongside the restructuring to raise the quality of research and education across the Faculty. In parallel with his leadership role Ian maintains some clinical activity and a large research programme. He specialised clinically as a surgical gynaecological oncologist but now limits his clinical work to familial cancer and screening. He directs a laboratory and clinical research team focused on genetics, proteomics, imaging and biomarkers in detection and screening for gynaecological cancers. He currently holds grant awards totalling over 25 million from Cancer Research UK, the Medical Research Council and the Department of Health. Ian is Principal Investigator on several large multicentre clinical trials including the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) involving 202,000 participants in 13 collaborating UK centres and the UK Familial Ovarian Cancer Screening Study (UKFOCSS). Dr Ian Waddell has been recruited as Head of Biology in the Drug Discovery Unit (DDU) at the Paterson Institute. Ian joins the DDU from AstraZeneca s oncology department where he was Director of Discovery Medicine focusing on translational science, a field which complements work currently undertaken in the Paterson Institute s Clinical and Experimental Pharmacology (CEP) Group, led by Professor Caroline Dive. The proximity of the DDU to groups like the CEP, and the availability of the MCRC s clinical expertise, will provide access to resources and experience that will facilitate Ian s research efforts and hopefully offer the DDU new drug targets. His focus will be on ensuring that the biological support for optimising a portfolio of drug hunting targets is in place through enhanced target selection and optimised target validation, identifying and developing those that have the most potential to impact patient outcomes. Ian has over 18 years experience in the pharmaceutical industry and broad experience in all stages of modern drug discovery having managed large discovery based groups in both cardiovascular and oncology disease areas. 5

6 Recognition of Outstanding Translational Research Team at the MCRC A major highlight this year has been the award of Cancer Research UK s Translational Cancer Research Prize to a team of MCRC researchers in recognition of outstanding translational research. Announced in November 2011 at the National Cancer Research Institute (NCRI) Annual Conference, the research grant of 25,000 is given to truly collaborative research teams that have made novel and influential cancer research discoveries that have had significant impact on the prevention, diagnosis and cure of cancer. The award recognises a team of four researchers: Professors Caroline Dive, Malcolm Ranson and Andrew Hughes and Dr Fiona Blackhall. It does not reflect a single identified accomplishment, such as a specific drug discovery and development project or a high profile clinical trial. Instead, it recognises the demonstrable transformation of landscape within the MCRC in its capacity to deliver high quality, high volume, timely, biomarker incorporated clinical trials and the significant, pioneering contributions to this rapid evolution by each of the four team members. This transformation allows multidisciplinary team working to flourish, linking research within the Clinical and Experimental Pharmacology (CEP) Group at the Paterson Institute with clinical trials and pharmaceutical drug development, which has been exemplified through close collaboration with AstraZeneca, pioneered by Professor Hughes, Vice-President of Clinical (Innovative Medicines, Oncology) at AstraZeneca and Professor of Translational Medicine within the School of Cancer and Enabling Sciences. This is a seamless and rational approach that is critical in establishing a truly bench to bedside enterprise, said Professor Dive, CEP Group Leader. 6

7 Delivering high quality, high impact clinical and translational research, conducted to Good Clinical Practice (GCP) and is reliant upon close multidisciplinary team working. The integration achieved by the MCRC has been widely regarded a shining example of high quality cancer care linked with world class team science, said Professor Ranson, Professor of Medical Oncology and Pharmacology within the School of Cancer and Enabling Sciences. Early phase clinical trials are closely aligned with translational research and the last few years have seen Manchester become one of the most active early phase clinical trial centres in Europe. The Manchester Experimental Cancer Medicine Centre (ECMC, with Professors Ranson and Dive as Principal Investigators) received a Forefront score by the CR-UK site visit panel for past and future research and was recently awarded a grant of 500,000 per annum for the next five years. The opening of the expanded Clinical Trials Unit (CTU) within the new Patient Treatment Centre at The Christie in November 2010 was the outcome of a synergistic strategy for research and service chemotherapy delivery. Within this strategy we acknowledged the importance of providing integration of novel insight from biomarker research - over 80% of the early phase trials conducted in the CTU include additional biological sample collection and, in the last 12 months, this figure hit 100%. Our early phase research helps to define potential biomarkers to assist dose optimisation, improve patient selection and develop logistics for translational research in larger patient cohorts, said Professor Ranson. A growing trend of cross-cutting research has emerged in which advanced biomedical imaging is combined and compared with serial blood and tissue borne biomarkers. These studies should help optimise future patient treatment particularly for targeted agents. To support the future growth of translational research the MCRC has also recently invested in informatics and this year saw the development of a Laboratory Information Management System to cover the GCP laboratories at the Paterson Institute and CTU, providing powerful linkage and management tools for large clinical and research laboratory datasets. After just nine months of opening, the CTU is fully operational and the focus has turned from provision of excellent facilities to attracting and recruiting world class researchers. Senior Clinical Lecturers with expertise in experimental medicine and translational research are rare and historically there has been a dearth of well trained clinical and translational scientists in Europe. To address this need a two pronged approach is being taken: external recruitment and a grow your own initiative. Since 2006, a highly successful Clinical Pharmacology Fellowship scheme funded by Cancer Research UK and AstraZeneca has enabled 10 promising young clinical researchers to develop and hone their research skills in early phase clinical trials and experimental pharmacology and to undertake PhD training. Five years on, the scheme is now delivering results - of the first four who have completed a PhD, three have been awarded National Institute of Health Research (NIHR) Clinical Lectureships within the MCRC and the fourth has already secured a substantive consultant post. The scheme has also been complemented by The University of Manchester s MRes in Translational Medicine, which was established by Professor Hughes. Continued investment in future research talent remains a key objective. We now have facilities, expertise and resources in Manchester that would be very hard to find elsewhere. With a flourishing CEP team, as well as imaging, Biobank and drug discovery we are very well placed to attract and retain outstanding talent, said Professor Ranson. Professor Dive also emphasised the importance of the training schemes: They provide the young medical oncologists needed to develop and understand the science that underlies individualised medicine, she said. 7

8 In addition to the prestigious Cancer Research UK Translational Cancer Research Prize, several notable achievements have been made in CEP within the last 12 months. Collaborative research with Dr Blackhall, a lung cancer specialist at The Christie who leads the MCRC s strategic implementation team for lung cancer research, has demonstrated that circulating tumour cells (CTCs) in patients with non-small cell lung cancer (NSCLC) and SCLC have value as prognostic and pharmacodynamic biomarkers. This finding could see the development of assays to measure these cells in order to identify optimal treatment options for individual patients and CEP is working with internationally renowned cancer centres on these cutting edge biomarker studies. Dr Radaslaw Polanski, a CEP postdoctoral researcher has been awarded a Cancer Research UK Research Travel Award to carry out research with Professor Tony Letai in the Dana-Farber Cancer Institute in Boston, Massachusetts, developing an assay in CTCs to predict drug sensitivity. Other collaborative research is underway jointly with Professor Anton Berns at the Netherlands Cancer Institute (NKI) in Amsterdam to apply CTC studies to mouse models of human lung cancer. Closer working between the CEP preclinical pharmacology team with the Drug Discovery Unit is developing well, enhanced by the arrival Dr Ian Waddell, the Unit s Head of Biology. The recruitment of Dr Stephen Walker, Translational Science Project Manager within CEP, to oversee the biomarker portfolio brings additional skills into the group in terms of pharmaceutical expertise. Dr Walker s recruitment complements the expertise in nucleic acid based biomarkers brought in by Dr Ged Brady. CEP recently signed a master research agreement with Abbott Pharmaceuticals to provide circulating biomarkers to their clinical trials demonstrating the tangible value of interaction with the pharmaceutical industry. The alliance of academic skills and pharmaceutical insight achieves progress in the drive towards personalised medicine driven by the individual characteristics of the patient s tumour. Until now CEP validated biomarkers have played a retrospective role to identify relationships with patient outcomes. Going forward, we will be increasingly using biomarkers prospectively to inform patient management decisions said Professor Dive. 8

9 National Role for MCRC Director On 1 February 2011, Professor Nic Jones was appointed Cancer Research UK s Chief Scientist, a role to which he will devote around half of his time. At the same time, Nic stepped down from his position as Director of the Paterson Institute. However, he will continue to lead the Cell Regulation Group which studies the nature and regulation of stress response pathways and their role in development, tumourigenesis and the protection of cells from environmental damage. He will also remain Director of the MCRC. Professor Jones said: I m delighted and honoured to be joining Cancer Research UK as its Chief Scientist. I have had the benefit of Cancer Research UK funding for many years and have first hand experience of the impact of the important work that this charity supports. The role of Chief Scientist will provide me with the opportunity to help shape the future research strategy and direction of this great charity. Cancer research is evolving rapidly and it is a particularly exciting time to be involved - there is the real prospect of a new era of cancer treatment through a more personalised medicine approach. Nic Jones has also recently been awarded the Gibb Fellowship. This is the most senior honour granted by the Gibb Fund and recognises outstanding researchers who have given, and continue to give, considerable service to the wider area of cancer research. Under the terms of his will, James Gibb left a life interest in his estate to his widow. When she died in 1961 the major beneficiary in her will was The Cancer Research Campaign (now Cancer Research UK) and a separate endowment trust fund was established. There are currently four Gibb fellows: Professor Nic Jones; Professor Sir David Lane, Chief Scientist of A*STAR in Singapore; Professor Chris Marshall, Director of the Cancer Research UK Programme on Tumour Cell Signalling Networks at the Institute of Cancer Research; and Professor Sir Bruce Ponder, Director of the Cancer Research UK Cambridge Research Institute. 9

10 Drug Discovery Unit Running at Full Speed The past 12 months have seen some key achievements within the Drug Discovery Unit (DDU) at the Paterson Institute with expansion of the team, establishment of a robust infrastructure and, most importantly, the prosecution of novel drug discovery projects. The Unit now has an active portfolio of drug discovery projects targeting a range of different cancer types including central nervous system tumours, leukaemias, lung cancer and also projects aimed at enhancing the anticancer effects of radiotherapy and chemotherapy. With the completion of the purpose built laboratory in December 2009, bench work began in January 2010 with a core team of 9 scientists. We have now expanded the team to its full working capacity with 23 staff including bioscientists, medicinal chemists and a specialist computational chemist. Dr Ian Waddell has recently been recruited to head our bioscience team in a key role which spans from drug target selection through to the translational interface with the Clinical and Experimental Pharmacology (CEP) Group at the Paterson Institute, ensuring that targeted molecules reach their potential, said Dr Ogilvie who heads the DDU. To assist in the identification and development of the most promising of these targeted molecules, the Unit has invested in state-of-the-art computational chemistry facilities. A significant application of this capability is to carry out virtual screening, which allows the visualisation of small molecule/target protein interactions and aids identification of molecules that may have biological activity and can be earmarked for further study. Much of the bench research that takes place in the Unit relies on the design and synthesis of very small amounts of novel molecules and this in itself can represent a 10

11 logistical and handling challenge. The solution has been to invest in highly specialised equipment including an acoustic dispensing system. Acoustic dispensing technology allows us to transfer tiny amounts of liquid on the scale of nanolitres - that is one millionth of a millilitre - using sound waves to propel the liquid sample out of an open source well. This does away with pipettes and traditional techniques and means we can dispense very accurately minute volumes and minimise waste, maximising the efficiency of our chemical synthesis and biological testing, said Dr Ogilvie. The laboratory is now fully equipped with purification and analysis systems such as nuclear magnetic resonance (NMR) spectroscopy and has invested in technology that can speed up throughput of novel small molecules. A major achievement this year has been the establishment of an informatics infrastructure, which underpins all the work carried out at the Unit. Managing the large amounts of data generated by their studies is a significant challenge as the data needs to be recorded using methods appropriate to support patent applications for successful compounds. The system they now have in place has been tailor made for their needs through a process of testing and refinement. The Unit s informatics solution allows them to develop electronic signatures that make the compounds legally identifiable. Collaboration both within the MCRC, via basic and translational scientists and clinicians, and with external partners beyond Manchester, is critical to the work carried out in the Unit. The breadth of opportunities and the strength of these collaborations is a direct result of the location of the DDU and its proximity to cancer research expertise. A motivating drive for our work is the direct line of sight to the clinic - being on this site gives us an invaluable understanding of how potential drugs could be used. Unlike pharmaceutical companies our focus is solely on patient benefit and unmet need rather than commercial viability but we also have access to specialist advice and support where commercial value can be established, explained Dr Ogilvie. to ensure that any commercial benefits are shared. CRT support is very valuable - it allows us to focus on the science and securing the best collaborations while still protecting our intellectual property rights. Crucially we have a local link through Dr Martyn Bottomley, CRT Business Development Manager, which allows for face-to-face direct involvement when needed. Another key advantage is that CRT provides a window to the world beyond our research enabling rapid exploitation of our discoveries so that these can be developed and taken out to patients as rapidly as possible. This timely translation of basic science to patient treatment and benefit lies at the core of what we aim to do here, said Dr Ogilvie. This specialist advice comes from Cancer Research Technology (CRT), the cancer focused technology development and commercialisation arm of Cancer Research UK, which provides an important interface for all the Unit s research. The advice includes guidance for the development and negotiation of robust agreements that are put in place for collaborations so that there is a clear understanding from project start on outcomes, ownership and modes of working 11

12 I is for Innovation and Imaging This year researchers in Clinical Imaging were awarded an Innovative Medicines Initiative (IMI) grant to lead one of the work packages, which aims to drive innovation in healthcare by supporting collaborative research projects and building interactions between industrial and academic experts. With a budget of 2 billion, IMI is Europe's largest publicprivate partnership and is a joint initiative between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The QuIC-ConCePT (Quantitative Imaging in Cancer: Connecting Cellular Processes with Therapy) group has been awarded an IMI grant to study imaging biomarkers for anticancer drug development. One of the key aims of QuIC-ConCePT is to qualify imaging biomarkers of tumour cell proliferation, programmed cell death (apoptosis), and necrosis - death due to disease, injury, or inadequate blood supply. The objective is to provide a suite of robust and validated imaging biomarkers that can be used by drug developers to demonstrate changes in these pathologic processes in tumours in patients in cancer clinical trials. Biomarkers of tumour cell proliferation and necrosis will be developed using imaging techniques such as positron emission tomography (PET) incorporating tracers, and magnetic resonance imaging (MRI). As less is currently known about robust tracers for apoptosis, initial studies will use PET tracers but the project has been designed to allow incorporation of additional or alternative apoptosis tracers as the project evolves. A more exploratory objective of QuIC- ConCePT is to use innovative approaches to devise, evaluate, and introduce imaging biomarkers of invasion and metastasis. The overarching aim of projects supported by IMI is to enhance discovery and development of better medicines for patients. QuIC-ConCePT has been given a unique opportunity to deliver tools which will markedly 12

13 improve drug development and benefit cancer patients not only in Europe but worldwide, said Professor Alan Jackson, who leads clinical imaging at the MCRC and is based at the Wolfson Molecular Imaging Centre (WMIC). MRI uses magnetic fields and radiofrequency pulses to provide detailed images of structures and tissues in the body. MRI is able to differentiate between the different soft tissues of the body and is therefore especially useful in brain, cancer and cardiovascular imaging. Dynamic contrast enhanced MRI (DCE-MRI) uses intravenously injected contrast material to make specific organs, blood vessels, or tumours easier to visualise. A key focus of clinical imaging research within the MCRC is on refining methods of image analysis and work on the development of a novel and improved DCE-MRI-based technique is due to be published this year in Magnetic Resonance in Medicine. Traditional DCE-MRI has limitations in terms of spatial resolution, temporal resolution and volume coverage. The new technique, ICR-DICE (Improved Coverage and spatial Resolution - using Dual Injection for dynamic Contrast Enhanced MRI) overcomes these limitations and provides high spatial resolution 3D pharmacokinetic maps with whole brain coverage and greater parameter accuracy than was possible with conventional methods. ICR-DICE has the potential to be very valuable in providing biomarkers for understanding vasculature changes in brain tumours such as acoustic neuroma. ICR-DICE enables routine use of DCE-MRI methods to patients with small brain tumours but also provides full brain coverage for examination of other lesions, including multiple discrete lesions, and larger, invasive lesions. Our aim is to further enhance this technique so that it can be used as an effective clinical tool and in the development of future drug treatments, said Professor Jackson. The research is to be featured as a keynote lecture at the World Skull Base Tumour Conference in 2012 and has generated widespread interest. the development of more accurate image reconstruction algorithms for PET. It also requires the development and use of tracer ligands and there is a need to find more PET ligands to aid in the diagnosis or staging of a variety of disease states. We have invested in a new system that allows us to produce PET ligands very rapidly. We can then evaluate these with the aim of developing robust tracers that have clinical utility, said Professor Jackson. Within the MCRC, imaging research is carried out by teams at the WMIC and the Faculty of Medical and Human Sciences. Clinical imaging at MCRC continues to flourish with investment in both facilities and researchers in order to drive development of clinically-useful imaging technology for cancer research and cancer patients. Other research within the team has demonstrated that DCE- MRI biomarkers of tumour heterogeneity can predict metastasis shrinkage following anti-angiogenic therapy with bevacizumab in combination with chemotherapy in patients with metastatic colorectal cancer that has spread to the liver. The research provides evidence that imaging biomarkers can predict response to therapy and as such could facilitate the development of a more personalised medicine approach with identification of patients most likely to benefit from specific treatments. Notable progress has also been made in 13

14 Preclinical Imaging Thriving evaluation of cell population dynamics (in particular cell proliferation and cell death) and the tumour microenvironment. PET-based tracers of proliferation and metabolism are being used as biomarkers for targeted therapies and preliminary grant funding has been secured for several small projects with industrial partners and sponsors. With the leadership of Dr Kaye Williams and active collaboration from preclinical magnetic resonance researchers, significant advances have been made in preclinical imaging over the past year. The MCRC now has a thriving and active preclinical imaging portfolio involving both positron emission tomography (PET) and magnetic resonance imaging (MRI) as investment in this important area has continued over the past 12 months. A state-of-the-art PET/computerised tomography (PET/CT) has been installed within the Wolfson Molecular Imaging Centre giving researchers access to a facility that was not previously available within The University of Manchester. PET/CT scans are very valuable - they provide images that allow us to accurately identify the location of aberrant metabolic activity within the body - images that are more accurate than either technique used alone. Access to this type of technology is crucial to developing our preclinical capability and expertise, said Dr Williams, from the School of Pharmacy. Current cancer research programmes using PET are focusing on the One example of successful working with industry that helps to drive research forward is the development of a strategic partnership with GE Healthcare UK. This collaboration has provided access to novel molecules for the study of certain processes that are important in tumour development, said Dr Williams. Dysregulation of programmed cell death is a critical process in cancer development. The in house radiotracer development programme has led to the development and validation of a new tracer, ML10, which can now be used to evaluate these apoptotic processes. Further collaborative studies with the Clinical and Experimental Pharmacology Group at the Paterson Institute have been carried out using genetic switch cancer models, which allow precise control of proliferation and cell loss. These tumour models will enable future validation of imaging biomarkers across multiple modalities. An additional research area that has just been initiated is within the evaluation of the tumour microenvironment, and in particular the assessment of inflammatory cell populations such as macrophages. Noninvasive imaging of inflammatory populations has far reaching applications within oncology and once fully validated is anticipated to be used by multiple groups, explained Dr Williams. The main focus of current preclinical MR activity is within oxygen enhanced (OE), diffusion weighted (DW) and multinuclear MRI. Capability in dynamic contrast enhanced MR, which uses faster imaging in combination with contrast material to improve visualisation of tumour tissue and associated blood supply, was also developed during The group undertook preliminary multi-nuclear MRI studies alongside PET, demonstrating the logistical feasibility of multi-modality imaging. The aim is to further develop this technique so that it can be used to validate DW-MRI parameters that provide some indication of cell death. One way of monitoring the degree, quality, or condition of cells present in a tissue is by monitoring the movement of water 14

15 or the apparent diffusion coefficient (ADC). Initial experiments show that radiotherapy treatment can induce a significant increase in ADC. We are now carrying out histology and advanced image analysis to gain insight into the biological mechanism behind this radiation induced change in ADC, said Dr Williams. Also this year, work on cerebral tumours led to the development of an orthotopic glioma model, which has important and exciting translational implications. In addition, a model of colorectal liver metastases has been developed and validated to provide a bridge to clinical studies. Biobank is Tried, Tested and Successful Now with around 2,200 samples available for cancer studies, the MCRC Biobank has become an established and valuable research resource. Since becoming fully operational, 41 projects requesting access to Biobank material have been submitted and 33 of these have been approved. We have a robust and efficient process in place for providing researchers with the high quality biological samples they need. We aim to review submitted proposals within 30 days and are on target with a median turnaround time of 26 days so that research time is not taken up waiting for a decision, said Professor Noel Clarke, Director of the MCRC Biobank. The Biobank has served as a vehicle for a number of tissue microarray research projects designed for high throughput analysis and expanding this service is a key goal. Working with the Lung Cancer Research Group, the Biobank will provide the facilities and skills central to the MCRC being a clinical hub for lung cancer within Cancer Research UK s Stratified Medicine Programme. The Biobank has been selected to undertake collection of 450 samples over two years in the first pilot phase of the Programme. They will be collecting and preparing tissue sections, blood samples and other biological material and sending them to the University Hospital of Wales where DNA will be extracted for genetic analysis. The ultimate aim of the programme is to link genetic data with clinical data and to provide information at the genetic level which may identify patients at risk of specific disease or complications, for example side effects, or most likely to benefit from a particular therapy, explained Professor Clarke. The pilot study will test the logistics of the approach and determine whether this is feasible and reproducible on a larger scale at the national level. Being chosen as the clinical hub for lung cancer for a project with national relevance and importance reflects the tried and tested process we have established here. It also reflects the strength of the lung cancer collection and of our relationship with lung clinicians within the MCRC partnership, said Professor Clarke. 15

16 New Researchers and Fresh Opportunities for Radiation Related Research The commitment of the National Cancer Research Institute (NCRI) to radiobiology and radiotherapy led to the establishment of the Clinical and Translational Radiotherapy Research Working Group (CTRad). CTRad aims to develop a range of practice changing trials and to optimise coordination of radiobiology and radiotherapy research with translation of new discoveries into practice. It has four discrete workstreams, each of which is chaired by two co-chairs to bring together different core disciplines. In November 2010, Professor Tim Illidge from the School of Cancer and Enabling Sciences was appointed Chair of CTRad - a three year appointment that reflects the high quality radiation related research (RRR) undertaken at the MCRC. Dr Kaye Williams, from the School of Pharmacy, cochairs the Science Base workstream which focuses on capturing relevant new discoveries in disciplines such as radiobiology, DNA repair, physics and imaging, while Dr Ranald Mackay, Director of North West Medical Physics, cochairs the New Technology, Physics and Quality Assurance workstream, driving the delivery of improved infrastructure support for radiotherapy trials in the UK. This October, Dr Williams organised a CTRad Imaging in Radiotherapy Research Workshop focusing on preclinical radiotherapy. The workshop aimed to provide a concise 16

17 overview of the range of imaging research being undertaken and how it can be applied to the radiotherapy setting, an understanding of the preclinical data needed to facilitate clinical transition, and to provide guidance and advice on the use of radiotherapy-based applications to improve imaging. In February 2011 Professor Ian Stratford, from the School of Pharmacy and Chairman of the LH Gray Memorial Trust, organised the 22nd International LH Gray Conference, Realising the potential of drug-radiation interactions in cancer treatment, which was hosted in Manchester. The meeting brought together basic and translational scientists with clinicians - facilitating discussion and sharing of experience so that new molecularly targeted agents increasingly used to treat cancer, can be fully evaluated in patients treated with radiotherapy. This was a truly international conference with speakers attracted from Europe, Canada and the USA and with good pharmaceutical representation which provides a different and important perspective that feeds into the clinical and scientific discussions, said Professor Tim Illidge. Dr Ranald Mackay has been heavily involved in the national Academic Physics Forum, which brought together representatives from 22 radiotherapy centres across the UK for a meeting in London in July. Organised under the auspices of CTRad, the meeting included a presentation by Professor Chris Moore, Head of Developing Technologies Radiotherapy Physics Section in North West Medical Physics, which highlighted the need for enhanced academic training in physics. A publication is being developed to provide a review of discussions from the meeting and also a paper to examine the challenges and solutions in developing academic physicists and exploring how best to build a base of trained academic physicists for future radiation related research programmes. disease control. This technique has advantages over conventional radiotherapy as it is more sparing of normal tissue and is therefore commonly used to treat tumours that are surgically inaccessible. The programme for investigating CNS tumour radiotherapy is a good example of the collaborative approach which underpins radiation related research at the MCRC. We will be working with Salford Royal NHS Foundation Trust s neurosurgery unit who have expertise in the delivery of radiotherapy to CNS tumours and Dr Whitfield will be able to link with physics groups to focus on advanced radiotherapy delivery to these tumours, said Professor Illidge. Proton therapy is a highly targeted, particle physics-based treatment that is currently not available in the UK but has had promising results, and may be especially useful in treating tumours of the CNS. The past 12 months has also seen the development of novel preclinical models of cancer that more accurately reflect the true situation of cancers in patients. These models are essential for testing new hypotheses and techniques before clinical investigation can be undertaken to assess efficacy and safety in volunteers and patients. Developing more realistic models of cancer that have the characteristics, environment and behaviour of real tumours allows us to better bridge the gap between laboratory-based and clinical research through translational activity. We aim to develop our expertise and skills in this area in order to drive internationally important research with novel radiation-drug combinations and radiation modelling, concluded Professor Illidge. One of the areas of greatest progress has been the integration of research staff into the clinical oncology department, a strategy which has been greatly facilitated by Dr Nick Slevin, Director of Clinical Oncology at The Christie. This has included the development of an academic clinical fellow scheme and the ongoing appointment of tumour group leads. Recently Dr Gillian Whitfield was recruited as a Lecturer and Consultant to lead the Central Nervous System (CNS) Tumour Research Group at The Christie, focusing on advanced radiotherapy delivery. The group will be exploring delivery techniques such as stereotactic radiotherapy, which uses computer imaging to more precisely direct radiation into the tumour from multiple angles to achieve local 17

18 Breadth and quality of MCRC lung cancer research continues to grow The World Conference on Lung Cancer (WCLC) is hosted every two years by the International Association for the Study of Lung Cancer (IASLC) and represents a key meeting for researchers in lung cancer and thoracic malignancies. Work presented by the MCRC s Lung Cancer Research Group at this years conference highlights how the group has evolved to contribute to understanding and treatment of lung cancer at a national and international level. The WCLC was held in Amsterdam in July 2011 and attracted over 7,000 delegates, with more than 1,880 abstracts being submitted; only a fraction of these were chosen for poster presentation and even fewer for oral presentation. This is the first year we have had such a large number of abstracts accepted for presentation. MCRC lung cancer researchers were involved in seven oral presentations and 15 posters. The research presented demonstrated the diversity of expertise in the group covering basic research, early detection, translational and biomarker studies, said Dr Fiona Blackhall, a lung cancer specialist at the The Christie. One oral presentation, coauthored by Dr Paul Lorigan, a Senior Clinical Lecturer within the School of Cancer and Enabling Sciences, was rated a top oral abstract and was included in the Conference President s selection. The abstract reported on a phase 3 trial comparing standard topotecan chemotherapy with amrubicin, both of which work by disrupting DNA replication. Another oral presentation presented phase 2 data for crizotinib - a treatment specifically for patients with advanced lung cancer who have a genetic rearrangement of the anaplastic lymphoma kinase (ALK) gene. Crizotinib was granted fasttrack review by the US Food and Drug Administration (FDA) last year and in August this year was approved by the FDA, highlighting the rise of personalised medicines. Dr Philip Hasleton, formerly consultant pathologist at University Hospital of South Manchester (UHSM) NHS Foundation Trust, received the IASLC Mary Matthews Award for lifetime scientific achievements in pathology translational research of thoracic malignancies. Dr Jian-Mei Hou, a postdoctoral researcher in the Clinical and Experimental Pharmacology (CEP) Group at the Paterson Institute, received a Fellowship Award for her abstract on the molecular characteristics of circulating tumour cells (CTCs) and circulating tumour microemboli in patients with lung cancer. Finding biomarkers that can tell us about the likelihood of an individual patient responding to a particular therapy, and therefore tailoring treatment to individual patients, is a major focus of lung cancer research. There have been many studies on CTCs and their potential to act as easily accessible blood-borne biomarkers. We have been working closely with researchers in CEP and have had some very encouraging results this year, said Dr Blackhall. Findings from their study investigating CTCs in patients with nonsmall cell lung cancer (NSCLC) were published recently in the Journal of Clinical Oncology. They demonstrate for the first time that CTCs in patients with advanced NSCLC can indeed provide prognostic information and also an early indication of likely patient response to conventional therapy. This research is a prime example of what we set out to achieve - using findings in the laboratory to ask and answer clinicallyrelevant questions that impact patient treatment, said Dr Blackhall. The next crucial step is to validate these results and then to develop CTC detection and analysis assays that can be used routinely in the clinical setting to inform treatment decisions. The importance of the translation of laboratory findings to useful clinical tools is highlighted by the group being designated a clinical hub for lung cancer by Cancer Research UK, a key achievement this year. The Stratified Medicine Programme aims to establish a national service for standardised high quality, and cost-effective genetic testing of tumours to allow routine identification of patients most suitable for particular targeted treatments. This designation has been facilitated by the establishment of the MCRC s Biobank, which is attracting an increasing number of lung cancer sample submissions from UHSM surgeons and pathologists. The first phase of the Stratified Medicine 18

19 Programme runs until 2013 and aims to develop a model for standardised collection and genetic testing with the chosen clinical hubs covering six tumour types; breast, bowel, lung, prostate, ovary and melanoma. The second phase will be the roll out of the service nationally. Mesothelioma is a relatively rare form of cancer that often develops in the lining of the lung. The Lung Cancer Research Group have been awarded a new grant from Research for Patient Benefit (RfPB), a national initiative set up in 2006 to support high quality research for the benefit of users of the NHS in England. The grant is for the phase 3 PIT trial which aims to evaluate the role of prophylactic irradiation to the chest wall after invasive procedures in patients with mesothelioma. Currently, use of prophylactic irradiation varies across the UK and the trial, which is being led by Dr Neil Bayman, Consultant in Clinical Oncology at The Christie, should provide important information that has the potential to change and standardise clinical practice. Alongside their basic, translational and clinical research, the group is also investing in improving understanding of the disease mechanisms in lung cancer and Dr Daisuke Nonaka, Consultant Histopathologist at The Christie, has recently been appointed as an Honorary Senior Lecturer within the School of Cancer and Enabling Sciences, to strengthen the academic breadth of the group. We have seen an outstanding level of high quality research over the past 12 months and continue to grow our knowledge and skills base in lung cancer. The WCLC demonstrated just how much progress we have made as a group, said Dr Blackhall. 19

20 Manchester Breast Centre Tackles Risk Prediction Identifying women who may be at higher risk of developing breast cancer remains a major focus of research at the Manchester Breast Centre. The PROCAS study - Predicting Risk Of Cancer At Screening - aims to recruit 60,000 women who attend routine NHS breast screening in Greater Manchester in order to predict breast cancer risk. Professor Gareth Evans, Consultant in Medical Genetics and Cancer Epidemiology at Central Manchester Hospitals NHS Foundation Trust, was recently appointed Director of the Manchester Breast Centre. He leads PROCAS, the largest study of its kind in the UK, which uses a combination of standard risk factors, such as family history, lifestyle factors, breast density (assessed through mammographic data) along with genetic factors revealed through identification of minute changes in DNA sequences known as single nucleotide polymorphisms (SNPs). Women taking part in the study complete a simple two page questionnaire, have a mammogram and then provide saliva for DNA testing. Mammographic density is one of the strongest risk factors for breast cancer but we still need to optimise how we use this information in risk algorithms to better identify women who are at higher risk of developing breast cancer, explained Professor Evans. By combining this with potentially more specific genetic information from SNPs, the aim is to develop a more accurate and targeted approach to risk prediction. Recruitment to the PROCAS study ends in 2012 and so far 32,000 women have been entered. DNA from these participants will be compared with those from a control group and used to predict breast cancer risk. The team also has information from around 9,500 women screened in the past 23 years in the Manchester Family History Clinic (FHC), 20

21 400 of whom later developed breast cancer. They will be looking at this enriched risk population in order to identify potential differences that may be linked to cancer development and to evaluate predictive algorithms. The availability of biological samples for genetic analysis allows investigation of potential links between genetic alterations and cancer development. It has recently allowed researchers at the Manchester Breast Centre to evaluate the link between two tumour suppressor genes (BRCA1 and BRCA2) and risk for breast and ovarian cancer. This year they have generated data demonstrating that the increased risk for the two cancers combined is caused mainly by mutations in BRCA1 and BRCA2. They have recently also published their findings on the prevalence of BRCA1 and BRCA2 mutations in women with triple-negative breast cancer, where oestrogen, progesterone and HER2 receptors are absent on the tumour cells. This type of breast cancer typically has a poor prognosis and also is not amenable to treatment with receptor targeted therapies. Their study, published in August 2011 in the Journal of Medical Genetics, indicates that BRCA1 mutations are found in only around 10% of isolated cases in women aged under 40 years of age and as such BRCA1 mutation represents a relatively small risk in this disease setting. However, with a family history of breast or ovarian cancer the risks rise dramatically. They are now validating SNPs for BRCA2 to assess their predictive value in the FHC population and other cohorts. Also this year, the research team have published potentially practice changing data from a study showing that enhanced screening can increase overall survival especially with regard to BRCA2. In another study published in the August edition of the International Journal of Cancer, the researchers evaluated the effectiveness of early surveillance by mammography and clinical breast examination (CBE) by nurses. CBE contributed to around one third of cancer diagnoses, was able to detect tumours not readily detected by mammogram alone and was also cost-effective. Their results indicate that the combination of mammography and CBE may diagnose breast cancer in a less advanced state compared with symptomatic cancers and in some women may play a part in improving long term outcome compared with no surveillance. of our research aims to ensure that we have improved algorithms for predicting which women are at higher or lower risk of developing breast cancer. We can then direct resource to the most appropriate women, at the most appropriate time. The aim is to offer better advice to identified higher risk groups and also potentially more regular screening and closer monitoring. Optimising how we use resources to improve breast cancer prediction and treatment is increasingly important, and risk stratification is a rational approach to meet this objective, said Professor Evans. As Director of the Manchester Breast Centre, Professor Evans aims drive a cohesive strategy in breast cancer research, building on collaborative approaches to minimise duplication of effort and make the most of resources. Much 21

22 The Manchester Breakthrough Breast Cancer Research Unit Paul Lu, a developmental biologist within the Faculty of Life Sciences, is particularly interested in how stromal signals instruct epithelial structures of the developing breast. He has shown that the breast stroma (the supporting cells and connective tissue of the breast) is capable of transdifferentiating lung cells into a fully functional mammary tree. Elucidating the molecular mechanisms of the stromal instruction of the epithelium is likely to give important insights into the control of breast development. The Breakthrough Breast Cancer Research Unit in Manchester was formally opened in March Its overall aim is to translate laboratory findings into the clinic to improve the treatment and prevention of breast cancer but with a special focus, although not an exclusive one, on targeting epithelial stem cell-stromal interactions. The Unit comprises four Team Leaders: Professor Michael Lisanti (Director), Professor Göran Landberg, Dr Paul Lu and Dr Rob Clarke. In addition there are three Clinical Associates: Professor Nigel Bundred, Dr Sacha Howell and Professor Tony Howell, who was Director of the Unit until September Göran Landberg, Professor of Molecular Pathology within the School of Cancer and Enabling Sciences, is focusing on the effects of hypoxia (decreased oxygen supply) on stem cell function, the relationship between cell proliferation and invasion and also has established a molecular pathology platform, particularly, tissue microarrays. Michael Lisanti, Professor of Cell Biology within the School of Cancer and Enabling Sciences, is in the process of moving his laboratory from Philadelphia to the Unit and has already begun to establish a group. The major interest of the laboratory is in metabolic interactions between breast tumour cells and the stroma. His group have demonstrated that a major activator of tumour stromal fibroblasts is hydrogen peroxide released from adjacent tumour cells. In response to this increased hydrogen peroxide, epithelial tumour cells appear to instruct the tumour stroma to feed them stromal derived lactate and other energy rich biomolecules. Released hydrogen peroxide is also associated with increased NFKB synthesis and fibroblast cytokine release and reduced expression (downregualtion) of the cell surface signal transduction protein caveolin-1. Downregulation of caveolin-1 is an important marker of poor prognosis in breast cancer and presumably indicates aggressive tumours able to regulate the microenviroment to allow metastatic spread. The metabolic interactions outlined above may well lead to new avenues to therapy directed at the new processes discovered by Professor Lisanti s group, including the use of anti-oxidants and the anti-diabetic drug metformin, in the clinic. Robert Clarke, a stem cell biologist within the School of Cancer and Enabling Sciences, is involved in understanding how micrometastases are regulated in their environment, an insight that will aid the development of new strategies to inhibit their formation or progression. He will be investigating bone marrow metastatic niche cells and their effects on metastatic stem cell activity. In particular, he will determine the signals between stroma and cancer stem cells 22

23 (CSCs), improving our understanding of how they regulate dormancy or activity of CSCs in the metastatic niches of the bone marrow. Ultimately, the aim is to improve eradication of metastatic breast CSC potential during adjuvant treatment by targeting the metastatic niche interactions in combination with current standard therapies, said Professor Howell. (ranked number1 in Pathology). The Manchester Breakthrough Unit will be internationally peer reviewed in April Michael will lead the Unit through the peer review process and over the subsequent years. It will be important to build on the progress made to date and begin to translate our current discoveries into the clinic, said Professor Howell. The Clinical Associates of the Breakthrough Unit are particularly interested in new drug development in preoperative studies (Nigel Bundred), in advanced breast cancer (Sacha Howell) and for prevention (Tony Howell). In September 2010, Professor Lisanti was appointed as the new Director of the Manchester Breakthrough Breast Cancer Research Unit, taking over from Tony Howell. As well as the Directorship of the Unit, he holds the Muriel Edith Rickman Chair of Breast Biology within the School of Cancer and Enabling Sciences. Michael is currently listed amongst the Top 100 Most-Cited Researchers in Biochemistry and Biology in the world and is currently ranked number 23 world-wide. He has published over 385 papers and was recently named as the new Editor-in-Chief of the American Journal of Pathology 23

24 International Chromosome Conference Comes to Manchester The 18th International Chromosome Conference was hosted by The University of Manchester at their brand new state-of-the-art conference facility from 29 August -2 September This international meeting is held every two years, with the previous two meetings being held in Boone, Virginia, US and Amsterdam. The local organising committee, chaired by Dr Dean Jackson, from the Faculty of Life Sciences, was responsible for defining the structure of the meeting and inviting an excellent and outstanding group of top international researchers in chromosome biology. As well as a range of sessions covering all classical aspects of chromosome biology the conference also touched on topics that are beginning to explore in great depth how understanding the behaviour of chromosomes impacts on our health and lifestyle. Topics included nuclear dynamics, systems biology of genomes and gene expression, genomic medicine and chromonomics - the exploration of the role of high throughput technologies for analysis of chromosome function. Of major relevance to MCRC are aspects of genome instability that arise during mitosis. This session was introduced and chaired by the highly eminent world leader in mitosis research, Professor Conly Rieder from the Wadsworth Centre in New York, and included podium presentations from top experts in the field. The MCRC was delighted to sponsor Professor Duane Compton, from the Dartmouth Medical School in New Hampshire, US, who described his recent exciting work on how defects in mitosis play a major role in genome instability and cancer, a subject that lies at the heart of cancer biology, said Dr Jackson. The meeting also incorporated lectures that were open to the public and public outreach debates that focused on bioethical issues related to understanding our genomes and how genomic science impacts on disease treatment. The 320 attendees were offered an extensive programme of social and networking activities, posters, podium presentations selected from posters and specialist satellite events. 24

25 International Spring Conference Highlights Breast Cancer The International Association for Breast Cancer Research (IABCR), in partnership with Breakthrough Breast Cancer, is holding its 28th conference on April 2012 at the Palace Hotel in Manchester. Stromal-epithelial interactions in breast cancer development and progression aims to highlight the potential that targeting the stromal environment will have for improving breast cancer treatment and has attracted many international speakers. These include Professor Max Wicha, Director of the University of Michigan Comprehensive Cancer Center, US, who is well known for his research in the field of breast oncology, and Dr Mina Bissell from the Lawrence Berkeley National Laboratory in California, US, who has been recognised for her lifetime contributions within breast cancer research. Topics covered during the conference will include breast cancer development and progression, precursor lesions, invasive cancer and metastatic disease with an emphasis on the influence of the stromal environment. A stimulating mix of cutting edge experts and young investigators will be brought together to discuss the important role of stroma and its role in cellular adhesion, stem cell activity, migration and metastasis. Interaction and discussion is a key part of the conference and we have designed the programme to allow many opportunities for researchers to communicate their most recent data and diverse perspectives, said Dr Rob Clarke, IABCR President. In addition, participation from post-doctoral scientists and graduate students will be encouraged through the selection of short talks from submitted abstracts and dedicated time for poster sessions. The deadline for registration is Friday 16 March 2012 and more details are available at: 25

26 First Graduates From MRes in Oncology able to progress projects that would otherwise not be so far along, said Professor Saha. Caroline worked on the kinetics of asparaginase, a longstanding chemotherapy drug, assaying patients on clinical trials. Caroline produced some excellent data, submitted an abstract to an international conference and the aim is to develop a publication with her data. It was a very positive and beneficial experience for everyone involved and one I would be very happy to repeat given the quality of students we have been able to attract, said Professor Saha. This year the first medical students to successfully complete the new MRes in Oncology graduated, armed with the specialist knowledge and research skills to pursue a research career in oncology. The one-year full time programme was set up in September 2010 to provide postgraduate-level training for undergraduate medical students who had completed year 4 of their degree. Designed as a practical programme with a focus on clinically relevant skills, the course combined tutorials and lectures with opportunities to develop core practical laboratory skills working closely with MCRC supervisors. Vaskar Saha, Professor of Paediatric Oncology within the School of Cancer and Enabling Sciences, was one of the supervisors and welcomed the fresh perspective that his student, Caroline Fong, brought to the laboratory. I have always enjoyed teaching and it was very valuable to have an extra pair of enthusiastic hands in the laboratory - we were Dr Corinne Faivre-Finn, Clinical Oncologist and an honorary Senior Lecturer with a special interest in radiotherapy for lung cancer, was also a supervisor for the MRes course. Her student, Jonathan Helbrow, focused his research on radiation related toxicity in lung cancer patients analysing data from around 100 patients from different databases to identify factors predictive of toxicity. Jonathan was very positive and motivated and was a pleasure to work with. He showed a lot of initiative and produced a very good quality thesis - having him here enabled us to conduct a study we could not have done in so timely a manner with existing resource, said Dr Faivre-Finn. She added that for would-be supervisors, having the time to review and provide guidance is very important and ensures that both the student and the team can make the most of the one year programme. MRes graduate Jonathan Helbrow first became interested in research as an undergraduate and realised that an intercalated degree could have career benefits. He has always had in interest in oncology and says that the course has had a positive impact on his overall knowledge and skills. The methodological approach you have to bring to research means that I am now far more analytical and my academic writing is stronger. I think I am also better organised and my time management skills have improved tremendously. It s an intensive and challenging course that provides transferable skills that will be of lasting value, he said. As a result of the MRes course he has had two poster presentations, one at a national and another at an international conference, two abstracts published and won a prize from the Royal College of Radiologists. In Jonathan s experience the programme is a steep learning curve but very rewarding and has confirmed his wish to pursue a career in academic medicine and clinical research. At the end of the course he applied for an 26

27 Academic Foundation post which gives young medics a four month research stint within their mandatory two year foundation training. The posts are very competitive as those accepted still need to attain a high level of clinical competencies within a shorter time frame. At the end of September, Jonathan heard that his application had been successful and he will be starting his Academic Foundation post at Salford Royal NHS Foundation Trust in Greater Manchester, where he hopes to carry on with research in oncology. The MRes Oncology programme has been really beneficial - I know what I want to do and I know from firsthand experience what this entails. The course has given me the skills and experience to make the most of opportunities in clinical research, said Jonathan. New Building Update Proposals for a new research building to accommodate the rapid expansion of high quality research at the MCRC have been finalised and submitted to Manchester City Council. The new MCRC laboratory research building will support the expansion of research activities with tremendous potential for future breakthroughs and help the MCRC to become a world leading comprehensive cancer research centre. It will also create a recruitment incentive to attract additional world class researchers in a deeply competitive international marketplace and allow the improvement and co-location of facilities and services on the MCRC site - helping us to use resources in the most effective way. Public consultation sessions were held in April and June, followed by a public meeting in September to share proposals and gather views for the new MCRC building and car park on The Christie site. The planning application was registered with the council at the end of October. Subject to Detailed Planning Approval being granted, work is planned to start during the first quarter of 2012 with completion of the MCRC building by the end of