£5 Million Stratified Medicine Programme Launched to Personalise Care For Bowel Cancer Patients

Cancer Research UK and the Medical Research Council  jointly launched a Stratified Medicine Consortium to help personalise bowel cancer treatment by matching patients to the most effective therapies, today. 

The £5M Stratification in COloRecTal cancer or S-CORT Consortium is made up of the following partners: University of Oxford; Queen’s University Belfast; University of Birmingham; University of Leeds; Wellcome Trust Sanger Institute; MRC Clinical Trials Unit; Kings College London; University of Aberdeen; University College London; Almac; Astra Zeneca; Glaxo Smith Kline; Beating Bowel Cancer; Northern Ireland Cancer Research Consumers Forum; European Organisation for Research and Treatment of Cancer; Cardiff University; Ku Leuven; European Alliance for Personalised Medicine; The University of Manchester; European Cancer Organisation. The funding for S-CORT is split evenly between Cancer Research UK and the Medical Research Council.

S-CORT will use the latest genome-based technology to uncover the complex biology of bowel cancer in samples collected from over 2,000 patients from large clinical trials. Researchers will use this information to precisely match the right treatment to the right patient. This approach will help better predict how different patients respond to treatment, allowing the most effective therapies to be delivered to newly-diagnosed bowel cancer patients.

These insights should help doctors decide which patients receive the chemotherapy drug oxaliplatin, what type of radiotherapy they’re offered, and may also help surgeons to remove as little of the bowel as possible.

More than 41,500 people are diagnosed with bowel cancer each year in the UK and treatment varies based on the type and size of the tumour, whether the disease has started to spread (metastasise), and on the health and fitness of each patient. This programme of research will identify and use new ways to predict the patient’s response to treatment based on the genetic make-up of their tumour, as well as helping doctors decide how to treat patients more effectively.

Professor Tim Maughan, Cancer Research UK Clinician at the University of Oxford and head of the S-CORT Consortium, said: “Bowel cancer survival has more than doubled in the last 40 years. But there’s still a lot more work to do. Recognising this challenge, we have brought together key partners from the UK and Europe in this consortium. Based on strong evidence from our previous work and generating new data from over 2000 individuals, we’ll identify ways to tailor treatment and ensure patients receive the drugs and other therapies that will benefit them the most, and make a significant difference to their chances of beating this common disease.”

Professor Mark Lawler, Chair of Translational Cancer Genomics, Queen’s University Belfast, said: “This precision medicine approach can maximise the effectiveness of both existing and brand new treatments while helping to minimise side effects, to improve survival and quality of life for our patients. Additionally, our health economic analysis will allow us to measure the benefit we can deliver for the NHS and the UK economy.”

Mark Flannagan, chief executive of Beating Bowel Cancer, a partner in the consortium, said: “We’re delighted to be involved in this innovative research programme, as it provides a route to improved care for our patients.”

The announcement is made during Bowel Cancer Awareness month (April) and represents a significant commitment from Cancer Research UK and the Medical Research Council (MRC) in developing more personalised medicine for cancer patients.

Peter Johnson, Cancer Research UK’s chief clinician, said: “We’ve a huge amount of new information coming through about the molecular changes that take place in bowel cancers, and we now need to understand how to match patients to the most effective treatments.

“Programmes like S-CORT will take the information we get from our clinical trials to a new level. We’ve made great strides in developing new treatments for bowel cancer, and around six in 10 patients now survive for more than 10 years, but we know there is more we can do.

“This programme will help establish a blueprint for new studies looking to tailor treatment for patients with other cancer types. It builds on existing work such as a pioneering clinical trial for patients with advanced lung cancer which launched last year.”

 

 

 

John Findlay wins Royal Society of Medicine Glaxo Travelling Fellowship

The CRUK Oxford Centre is delighted to announce that The Royal Society of Medicine recently awarded Centre member, John Findlay, its 2014 Glaxo Travelling Fellowship. John is a General Surgery Registrar in the Oxford Deanery, and a Senior Clinical Research Fellow in OesophagoGastric Surgery at the NIHR Oxford Biomedical Research Centre. His research interests focus on personalising therapy for patients with oesophageal and gastric cancer, on the basis of molecular, clinical and radiological biomarkers.

The 2014 Glaxo Travelling Fellowship was awarded for his paper ‘Novel classifications of oesophageal cancer FDG-avid nodal stage and metabolic response to neoadjuvant chemotherapy, and predicting progression to metastatic and unresectable disease’. This paper also won the 2014 Royal Society of Medicine Sylvia Lawler Clinical Poster Prize, and 2014 Association of Upper Gastrointestinal Surgeons of Greater Britain Poster Prize.

This study of 383 patients with oesophageal cancer treated in Oxford at the Churchill Hospital aimed to determine the utility of restaging oesophageal cancer after neoadjuvant chemotherapy with positron emission tomography-computed tomography (PET-CT), and was undertaken as part of John’s PhD. PET-CT was shown for the first time to be twice as sensitive as CT for detecting interval metastases after neoadjuvant chemotherapy for oesophageal cancer, with decision theory supporting routine re-staging PET-CT for all patients. In addition, new classifications of FDG-avid nodal stage and metabolic response to chemotherapy and predictive models were developed, which could identify patients at high risk of interval progression to metastatic or unresectable disease before surgery, and also those with a worse prognosis afterwards.

After his success with this paper John is now exploring whether PET-CT may have a similar predictive role in gastric and other gastrointestinal cancers. He commented that he was honoured to receive this prize on behalf of his collaborators, and hopes very much that these findings will have immediate use in counselling patients with oesophageal cancer, and also in identifying those patients who will benefit from additional staging and re-staging investigations.

CRUK Oxford Centre to Host International Symposium on Oesophageal Cancer

The Cancer Research UK Oxford Centre, Cancer Research UK, Cambridge Cancer Centre and Chinese Hospital Chinese Academy of Medical Science (CICAMS) have come together to host an International Symposium on Oesophageal Cancer.

The symposium is being co-organised by Professor Xin Lu, Professor Rebecca Fitzgerald and Professor Qimin Zhan. Speakers that cover the breadth and depth of Oesophageal Cancer Research will be in Oxford on June 6-7th for this innovative event.

We are pleased to confirm that registration is now open and details can be found here.

Why oesophageal cancer?

Investigating oesophageal cancer presents unique opportunities for advances on two fronts: addressing the substantial unmet clinical needs of this disease; and uncovering molecular mechanisms with broad implications for our understanding of tumorigenesis.

The oesophagus provides an unusual yet accessible tumour context. In the lower oesophagus, the squamous epithelium of the oesophagus meets the columnar epithelium of the stomach and oesophageal adenocarcinoma is often preceded by epithelial cellular changes in an inflammatory condition called Barrett’s oesophagus. This setting thus presents a unique model for studies of the fundamental principles of interactions among different epithelial cell types, how signalling and differentiation are disrupted in cancer development and the influence of immune responses and inflammation on cell fate. On a global scale oesophageal squamous cell cancer is a major cause of cancer related death with some very high incidence areas thus providing further opportunities for investigating the epidemiology and causation of this disease and potential avenues for treatment.

Oesophageal cancer research is thus an ideal forum to bring together cell biologists, geneticists, immunologists and clinicians.

World Cancer Day 2015

On World Cancer Day, 4th February, the Cancer Research UK Oxford Centre teamed up with 6 local charities to do a joint promotional activity in the Town Hall in Oxford. The event was attended by a mixture of charities including: Macmillan, Maggie’s Centre, International Network for Cancer Treatment and Research, Katherine House Hospice, Helen and Douglas House Hospice and Sue Ryder all of which represent the cancer patient journey, in Oxford and around the world.

Charlotte Richards, CRUK Research Engagement Manager says “It’s the first time that all these charities have worked together and it was a great day. A huge bonus was local councillors gaining interest in all the activity that’s happening locally and a good start for what we hope will become an annual event in Oxford. As a Centre, we hope to host many of the attendees on lab tours, so they can see the type of research that’s happening on their doorstep”.

If you’re interested in finding out more about lab tours then contact the Engagement team here.

Photo courtesy of Wendy Aldiss.

OCTRU Announced as an NCRI Cancer Clinical Trial Unit

The CRUK Oxford Centre is pleased to announce that OCTRU were successful in their application to become an NCRI Cancer Clinical Trial Unit. The basis for that application was the work they do in the Oncology Clinical Trials Office (OCTO), the oncology division of OCTRU.

In place of accreditation, an NCRI Cancer CTU Group has been established to bring together the field leaders that contribute at a national level to the advancement of cancer clinical trials, using simpler entry criteria that complement UKCRC registration.

Alongside OCTRU, a further 15 units were successful and a full list and further details of the scheme can be found here.

For OCTO, based in the Department of Oncology, this represents an opportunity to work with other cancer CTUs across the country to share best practice and improve the way in which cancer trials are delivered in the UK.

Sarah Pearson, OCTO Trial Management Director, commented: Thanks to increased funding from the CRUK Oxford Centre, OCTO has now restructured to create three portfolios of activity; early phase medical oncology, radiotherapy and imaging, and late phase trials. We have also established dedicated teams for data management and pharmacovigilance. This re-structuring has laid the foundations for providing support to increasing trials activity within the CRUK major centre and PCMI in the coming years. Completing the unit restructuring is a significant achievement for the whole OCTO team and we look forward to working on an increasingly varied portfolio of trials”.

To find out more about the outstanding work taking place in OCTO, visit their website or contact Sarah.Pearson@oncology.ox.ac.uk

 

Metal test could help diagnose breast cancer early

A team, led by Oxford University scientists, took techniques normally used to analyse trace metal isotopes for studying climate change and planetary formation and applied them to how the human body processes metals.

In a world-first the researchers were able to show that changes in the isotopic composition of zinc, which can be detected in a person’s breast tissue, could make it possible to identify a ‘biomarker’ (a measurable indicator) of early breast cancer.

A report of the research by the Oxford University-led team, which included researchers from Imperial College London and the Natural History Museum, London, is published in the Royal Society of Chemistry journal Metallomics.

The pilot study analysed zinc in the blood and blood serum of ten subjects (five breast cancer patients and five healthy controls) alongside a range of breast tissue samples from breast cancer patients. By using techniques that are over 100 times more sensitive to changes in the isotopic composition of metals than anything currently used by clinicians, the researchers were able to show that they could detect key differences in zinc caused when cancer subtly alters the way that cells process the metal. Similar changes in copper in one of the breast cancer patients is additional evidence that it may be possible to identify a biomarker for early breast cancer that could form the basis of a simple, non-invasive, diagnostic blood test.

‘It has been known for over a decade that breast cancer tissues contain high concentrations of zinc but the exact molecular mechanisms that might cause this have remained a mystery,’ said Dr Fiona Larner of Oxford University’s Department of Earth Sciences & CRUK Oxford Centre Member, who led the research. ‘Our work shows that techniques commonly used in earth sciences can help us to understand not only how zinc is used by tumour cells but also how breast cancer can lead to changes in zinc in an individual’s blood – holding out the promise of an easily-detectable biomarker of early breast cancer.’

The researchers say that this new understanding of cancer cell behaviour – in particular the role sulfur-containing proteins play in how tumours process zinc – could also help in the development of new cancer treatments.

‘The hope is that this research is the beginning of a whole new approach,’ said Dr Larner. ‘Understanding how different cancers alter different trace metals within the body could enable us to develop both new diagnostic tools and new treatments that could lead to a ‘two-pronged’ attack on many cancers. Further research is already underway to see what changes in other metals may be caused by other cancers.’

A report of the research, entitled ‘Zinc isotopic compositions of breast cancer tissue’, is published in the journal Metallomics.

Professor Gillies McKenna awarded the Gold Medal by the Royal College of Radiologists

In recognition of the outstanding contribution that he has made to the field of radiation oncology, CRUK Oxford Centre Director, Professor Gillies McKenna, has been awarded the Gold Medal by the Royal College of Radiologists. He also delivered the twelfth David Skeggs lecture, titled Imaging and Targets: The Molecular Frontiers in Radiation Oncology.

The Gold Medal is the most prestigious honour awarded by the Council upon the recommendation of the Honours Committee. Previous winners include Professor Peter Hoskin, Professor Dame Janet Husband DBE and Professor John Mallard. A full list of winners is available here.

Professor McKenna commented: “There is no higher honour that any clinician or scientist can receive than to be recognised by their peers. I recognise too that this is an acknowledgment that in the last ten years we have together brought back British radiation oncology and radiation biology research from a point where we wondered if it was going to survive as a discipline, to the point where we can proudly hold our heads high once more as world leaders. It has been a great privilege to me to have contributed to this revival, and I gratefully acknowledge the support I have received from the Royal College and its members in my work.”

 

Image reproduced with permission of The Royal College of Radiologists. Copyright Ede and Ravenscroft and RCR.

Reverse the Odds – Nominet Trust 100 Winner

Nominet Trust proudly announced that Reverse The Odds, an app that is helping CRUK Oxford Centre member Dr Anne Kiltie identify biomarkers in tumour samples, has been named among the 2014 Nominet Trust 100 (NT100) – a global list of 100 inspiring ventures from around the world.

Projects featured on the list are using technology to tackle some of the world’s biggest social problems from education and human rights abuses to climate change and health. Following a global call for nominations earlier this year Reverse the Odds has been selected by an independent steering committee in recognition of its fantastic game design, data analysis expertise and remarkable production that come together to allow citizen scientists to fight cancer. Reverse the Odds is the third Citizen Science project and has already analysed 2 million tumour samples. The game can still be played, visit the website to download the app and join in.

Commenting on their inclusion in the NT100, Dr Anne Kiltie said: “The app lets members of the public score our immunohistochemistry images for us. The public have already looked at one protein and we are about to compare the public’s scores with our ‘expert scores’ to see how well they match. There are other images in the app which are being analysed for a group in Southampton and their results are being compared at present, so the result is imminent”.

Annika Small, CEO of Nominet Trust, the UK’s leading tech for good funder, said: “There is a striking progression in the quality and maturity of this year’s NT100, indicative of a wider evolution in the ‘tech for social good’ sector as a whole. More people than ever before are using technology to solve problems that matter to them in bold new ways. This year’s NT100 list is populated by extraordinary people with inspirational stories to tell and it shows us that imagination, social conscience and technology make a potent mix to affect change.”

To see more about Reverse the Odds and the other Nominet Trust 100 winners visit the website.

 

Scientists Discover Why Bowel Cancer Sometimes Outsmarts Treatment

A new study that challenges the prevailing view of how bowel cancer develops in the large intestine is published today in Nature Medicine.

Cancer Research UK scientists have discovered that bowel cancer may not be restricted to starting its journey in the stem cells in the lining of the intestines as previously thought.

The researchers, based in Oxford at the Welcome Trust Centre for Human Genetics, studied a hereditary faulty gene which can cause bowel cancer in middle age. The faulty gene causes normal cells to behave like immortal stem cells and develop tumours of their own– challenging the theory that normal cells have a fixed fate and limited lifespan.

The cells lining the bowel are continuously replaced – new ‘daughter’ cells are produced by immortal stem cells to replace those that have worn out.

Many types of cancer are caused when chemical messaging goes wrong. Scientists analysed polyp samples from hereditary bowel cancer patients and found disruption of a key signalling pathway involved in stem cell control. They found the same problem in a wider selection of bowel cancer tumours. When they altered the key signalling molecule in the lab it caused daughter cells that had moved out of the stem cell zone to behave like stem cells and develop into tumours.

This could ultimately explain how some cancers become resistant to chemotherapy, as stem cells killed by the treatment may be continually replaced by cancerous daughter cells.

Simon Leedham, CRUK funded researcher at the Welcome Trust Centre for Human Genetics and CRUK Oxford Centre member, said: “This study has implications for drug development and tumour treatment. If these signalling pathways are disrupted in tumours then daughter cells could revert back to behaving like stem cells and then replace any cancer stem cells killed by chemotherapy”

“This may be one of the mechanisms behind tumour resistance to chemotherapy but could also represent a potential drug target. If we can restore the disrupted signalling balance in tumours then we may be able to stop daughter cells from replacing cancer causing stem cells and increase the effectiveness of our current therapies. ”

Professor Tim Maughan, Professor of Clinical Oncology and CRUK Oxford Centre Networking Lead, commented: “This new insight into the way bowel cancer develops is critically important. People with the type of cancer described may respond to different types of therapy and we can now test that in our sample sets from previous patients. Understanding the mechanism will help us design new approaches to treating this subgroup of patients to improve their outcome”

Read the more about the study, Aberrant epithelial GREM1 expression initiates colonic tumourigenesis from cells outside the crypt base stem cell niche, Davis et Al, here.

New Partnership Announcements

The Centre is excited to announce two large new partnerships in cancer research that will build on the world class, innovative work already taking place across Oxford today. Though administered through the Department of Oncology – these developments will impact research across our membership.

Greg Clark MP, Professor Gillies McKenna, Director of the Cancer Research UK Oxford Centre, and Andrew Hamilton, Vice-Chancellor of Oxford University, formally announced the Precision Cancer Medicine Institute (PMCI) on Thursday.
Through a £35m grant from grant from the Higher Education Funding Council for England (Hefce) and over £75m of investment in financial contributions and support in kind from partners in the project, the PCMI will ensure Oxford is able to undertake cutting edge research to further understanding of the genetic and molecular changes underlying a patient’s tumour, as well as trials of novel cancer drugs and the latest in surgery, advanced cancer imaging, and proton beam therapy.

The proposed partners include Cancer Research UK; Roche Diagnostics; GE Healthcare; Mirada Medical; Brandon Medical; Blue Earth Diagnostics; and the University of Florida Health Proton Therapy Institute. It is proposed that there will be a significant investment in the operation of a proton beam research facility within the new institute by ProNova Solutions, the intended US supplier of the proton beam equipment. All of the partners have been working closely with the team at the Cancer Research UK Oxford Centre to come together and create a new institute that will play a leading role in research in the future.

Professor Gillies McKenna, Director of the Cancer Research UK Oxford Centre, said: ‘The Precision Cancer Medicine Institute aims to improve outcomes and increase cure rates for cancer patients. It will do this not only by making surgery and radiotherapy more precise and less invasive, but by designing new drug treatments that are more targeted and personalised to the characteristics of a patient’s particular tumour, and by using advanced imaging techniques to detect the earliest signs of response. Through the new institute we aim to undertake research that will help doctors get the right treatment, to the right patient, at the right time.’

Cancer patients from Oxfordshire and nationwide will be able to participate in research studies in state-of-the-art facilities under the guidance of leading clinicians. During his visit to the Old Road Campus, Greg Clark commented: ‘Britain already punches above its weight in science and innovation globally. It’s only right that we harness this ability in the fight against cancer. This £110 million investment will help fund lifesaving research and create jobs.’

A new building to house the PCMI is likely to be constructed at the Churchill Hospital / Old Road Campus site in Oxford, but no firm decision has been made on a location.

Alongside the PCMI announcement, the creation of the Chan Soon-Shiong Oxford Centre for Molecular Medicine was also confirmed yesterday. A research partnership between the Chan Soon-Shiong Institute for Molecular Medicine in the USA and the University of Oxford will create a new centre where the latest techniques to characterise tumour samples from patients in order to understand the particular genetic and molecular changes underlying that patient’s cancer, leukaemia or lymphoma can take place.

The new Chan Soon-Shiong Oxford Centre is likely to be housed within the PCMI, where the clinical applications of its research will take place. It will work in close collaboration with the Oxford University Hospitals NHS Trust.
The Chan Soon-Shiong Institute has made an initial commitment of $50m (£31.2m) to advance these approaches to cancer medicine in the UK. Of this, $35m (£21.9m) in funding over eight years will establish the new research centre at Oxford University, supporting research and research positions. In addition, the Chan Soon-Shiong Institute will purchase $15m (£9.4m) worth of research equipment and data systems infrastructure in the UK, to which the University will be provided access.

The data will also provide a rich resource for cancer research, drive the development of new drugs and enable more ‘stratified medicine’ (where clinical trials are carried out in groups of patients that may be more likely to respond to a new treatment because of the particular characteristics of their cancer).

Dr Patrick Soon-Shiong, founder and chairman of the Chan Soon-Shiong Institute for Molecular Medicine, said: ‘Along with the University of Oxford, we are living our commitment to clinicians and patients alike. Using the most advanced, sophisticated tools imaginable, we’re on a mission to solve the mystery of cancer, and establish an adaptive learning system where the power of one can inform many. The infrastructure to manage big data must be established to enable a national network of clinical scientists in the UK and a portion of the $50m commitment will be used to fund the capital needs to ensure that patients throughout England could benefit from this genomic platform, with the remaining $35m provided to support the operations of the Chan Soon-Shiong Oxford Centre for Molecular Medicine at Oxford.’

These two new partnerships will work together with the Centre to deliver a vision of improved patient outcomes and help to place Oxford’s cancer research in a world-leading position well into the future.