Aspirin and acid reflux medication reduce the likelihood of patients with Barrett’s oesophagus developing oesophageal cancer.

Results of the AspECT clinical trial, coordinated by the CRUK Oxford Centre supported Oncology Clinical Trials Office, have shown the important role aspirin and acid reflux treatment can have in preventing those at high risk of oesophageal cancer from going on to develop the disease.

The trial led by Professor Janusz Jankowski had results presented last week at the American Society of Clinical Oncology conference. The trial investigated the chemo preventative effects of different doses of the antacid medication esomeprazole, with and without low dose aspirin in patients with Barrett’s oesophagus. Since acid reflux is involved in causing Barrett’s oesophagus it had been suggested that reduction of acid to very low levels might prevent progression to cancer.

The randomised phase III trial involved over 2500 patients who were followed for 7.9 years. Patients who followed a seven year course of high dose of esomeprazole with low dose aspirin, followed by high dose esomeprazole, were 20% less likely to develop oesophageal cancer than if they had been untreated.

Professor Janusz Jankowski, who completed an MSc in clinical trial research at Oxford University in 2009 and is currently Professor of Medicine at the University of Central Lancashire said: “Our results are very exciting. Oesophageal cancer is hard to diagnose and hard to treat. So, we’re pleased that such a cheap and well-established medicine can prevent and/or delay development of cancer for these patients. Our hope is that this may also offer an opportunity to prevent oesophageal cancer in wider populations.”

AstraZeneca – Oxford collaborative Symposium September 2018 – Registration open

We are delighted to announce a partnership symposium between AstraZeneca and the Cancer Research UK Oxford Centre, which will take place on September 13th 2018 at Keble College.

The primary aim of the event is to provide an opportunity for researchers from both organisations to get a better understanding of the research activities of the other, in order to establish a series of collaborative cancer research projects. Through the Centre Development Fund, financial support for projects emerging from the event will be available.

The event will include presentations on 4 core topics, DNA damage repair, radiation oncology, epigenetics and immunoncology and posters covering target identification and validation, CRISPR capabilities, early phase clinical trials, biophysics, structural biology, biochemistry/cellular assays and chemical probes.

There will be a range of speakers from both Oxford and AstraZeneca (see draft schedule below), and numerous opportunities for individual networking during breaks and at the drinks reception. We will be opening our next round of development funding at the event in order to support collaborations emerging from the event.

If you are interested in attending this free event, (open to group leaders, and post-doc’s across the University and Trust) and presenting a poster to showcase your research to AZ (and making yourself eligible for the poster prize) please register your interest here by Tuesday June 19th. Places are limited to 150 attendees and will be prioritised to those researchers presenting posters and those who register sooner.

Please note, all information included in the above application and presented at the conference will be considered pre-competitive, so bear this in mind when choosing which details to disclose.

 

 

Chris Holmes appointed Programme Director for Health Data in a partnership between Health Data Research UK and the Alan Turing Institute

We are delighted to congratulate Professor Chris Holmes, member of the Centre Management Group, on his new joint role for the Alan Turing Institute and Health Data Research UK (HDR UK).

Chris, who is Professor in Biostatistics at the University of Oxford, has considerable expertise in data science and artificial intelligence methodologies, specifically statistics and machine learning and its application to health and biomedical science problems. He has been employing computational statistics and machine learning approaches to integrate the multi-omics data (DNA sequence, methylation, transcriptome and patient records) generated by the S-CORT consortium to provide a greater biological understanding of colorectal cancer.

In his new role, Chris will facilitate direct scientific collaboration and leadership between the two national centres. He will develop and coordinate a programme of research involving collaboration across The Alan Turing Institute’s growing university network, creating opportunities with HDR UK’s six substantive sites and the broader health and data science sector. His programme will build on an already established set of health projects underway at the Turing, including partnerships with Cystic Fibrosis Trust applying machine learning to improve treatment plans, a set of interdisciplinary projects awarded jointly with the British Heart Foundation through the BHF-Turing Cardiovascular Data Science Awards and cross-cutting foundational research looking into data security and privacy.

Commenting on his appointment, Chris remarked:
“Already we are seeing data science and AI innovation bear fruit in the health sector; with areas like medical imaging now opening up to machine learning algorithms. There are many other areas of opportunity; including using data to inform adaptive clinical drug trials, personalised medicine, addressing operational challenges within the health service and using theoretical mathematics and statistics to help connect and understand the algorithms that can extract information from large datasets.”

“I am delighted to join with the Turing and HDR UK and look forward to working with these two national centres to improve human health and the scientific understanding of biomedical systems.”

Vincenzo Cerundolo and Neil Brockdorff elected as Fellows of the Royal Society

We a delighted to congratulate two Cancer Research UK Centre Members, Professor Neil Brockdorff of the Department of Biochemistry and Professor Vincenzo Cerundolo of the MRC Human Immunology Unit on their election as Fellows of the Royal Society. Fellows have made ‘a substantial contribution to the improvement of natural knowledge, including mathematics, engineering science and medical science’. Oxford University academics were well represented in this week’s elections to the Royal Society, with six of the new Fellows, more than any other single Institution.

On receiving the news, Professor Cerundolo said ‘I am extremely honoured and humbled to be receiving such an important recognition…. I am certain that working in the exciting and vibrant environment of the Weatherall Institute for Molecular Medicine and being able to collaborate with so many outstanding colleagues has contributed enormously to this achievement.’

Professor Cerundolo has strong collaborative links across the Centre and is undertaking work, supported through Centre and BRC NIHR funds, to understand complementary aspects of the immune response against solid tumours. His team are analysing the mechanisms by which tumour cells can evade immune responses focusing on expression of amino acid degrading enzymes; and the ability of tissue stroma to modulate the expression of tissue homing receptors expressed by T lymphocytes.

New initiative with the Synthetic Biology CDT

The CRUK Oxford Centre and Ludwig Institute for Cancer Research is pleased to announce a new initiative with the Synthetic Biology CDT which will provide 2 fully funded studentships (EU/UK rate) for students to join the 2018/9 Oxford–based cohort and go on to complete an interdisciplinary cancer-related project for their DPhil studies. Applicants with an interest in these studentships should describe and evidence their strong interest in the application of Synthetic Biology to cancer research in their application cover letter.

For more information please visit the link here.

Cancer Research UK Oxford Centre Announces Prof. Xin Lu as New Co-Director

The Centre is pleased to announce the appointment of Professor Xin Lu as Co-Director of the Centre, leading on the development of our scientific strategy. Professor Lu is an internationally recognised cancer biologist who combines ground-breaking laboratory research with experimental medicine. She has made major advances in understanding regulation of the tumour suppressor p53, revealing new ways selectively to kill cancer cells. Professor Lu is Director of the Oxford Branch of the Ludwig Institute for Cancer Research.

Professor Mark Middleton, Co-Director of the Centre, said: “I am delighted that Xin has agreed to join me in leading the Cancer Research UK Oxford Centre. Her expertise will be invaluable in developing the Centre’s strategy and in increasing engagement with fundamental science groups across Oxford. Her involvement in the NIHR Biomedical Research Centre and with the international Ludwig community will be great assets in our drive to make the most of Cancer Research UK’s investment here.”

David Scott, Director of Discovery Research and Research Communications at Cancer Research UK said: “Professor Lu’s appointment is fantastic news for the CRUK Oxford Centre; her skills and experience in leading the Ludwig Institute for Cancer Research Oxford will be invaluable to foster further collaboration and accelerate progress in translating cancer research for patient benefit.”

Simon Leedham awarded the Cancer Research UK Future Leaders in Cancer Research Prize

Today at the NCRI Annual Conference Professor Simon Leedham was awarded the Cancer Research UK Future Leaders in Cancer Research Prize.

Simon is a Cancer Research UK Clinician Scientist Fellow at the Wellcome Trust Centre for Human Genetics. His research has made important advances in the cell biology and molecular pathogenesis of gastrointestinal cancers and advanced our understanding of the role of BMP signalling in colorectal tumorigenesis.
In awarding the Future Leaders Prize to Simon, the selection panel from CRUK recognised his role in understanding the importance of the BMP antagonist, GREM-1, in colorectal neoplasia. This revealed a mechanism of hereditary polyposis and its importance in spontaneous colorectal cancer. Simon’s work has shown that cross-talk between conserved BMP signalling and notch, in a subtype of colorectal cancer, promotes poor prognosis. His more recent work is leading him into novel approaches to therapy.

The Panel regarded Simon to be a leader based on the quality of his research and his collaborative efforts, demonstrated by the number of prestigious conferences he has spoken at. The Panel considered Simon’s work to be widely recognised internationally, and that he is an excellent clinician-scientist, with strong leadership skills.

Awarding the Prize at the NCRI Conference, Sir Harpal Kumar noted the Panels confidence that Simon will continue to make significant contributions to the field and that these will drive cancer research forward.

Oxford University scientist developing new treatments to tackle breast cancer that has spread to the brain

Oxford University scientist developing new treatments to tackle breast cancer that has spread to the brain
Professor Nicola Sibson of the Department of Oncology has been awarded a grant worth almost £200,000 by research charity Breast Cancer Now to fund cutting-edge research to uncover novel treatment combinations to control breast cancer that has spread to the brain.
The news comes on Secondary Breast Cancer Awareness Day (Friday 13th October 2017), as leading charity Breast Cancer Now announces more than £700,000 of funding across the UK for research specifically targeting secondary (or metastatic) breast cancer – where the disease has spread to another part of the body.
When breast cancer spreads, known as secondary or metastatic breast cancer, it becomes incurable. While metastatic breast cancer can sometimes be controlled using different combinations of treatments, it cannot be cured, and almost all of the 11,500 women that die as a result of breast cancer each year in the UK will have seen their cancer spread. Nearly 600 women in Oxfordshire are diagnosed with breast cancer every year, and over 100 women in the region die from the disease each year.1
The brain is protected by its own security system, a structure called the blood-brain barrier (BBB). The BBB acts as a filter, preventing harmful substances from reaching the brain. However the virtually impenetrable nature of the BBB makes delivery of drugs to the brain extremely difficult, meaning there are few effective treatments for breast tumours that have spread to the brain (brain metastases).
Up to a third of patients with secondary breast cancer have seen their cancer spread to the brain. This can cause varying problems with brain function depending on which areas the breast cancer cells have spread to, and can often severely affect a patient’s quality of life, with debilitating symptoms such as changes in mood or behaviour, seizures, headaches, vomiting and uncoordinated movement.
Professor Sibson, Professor of Imaging Neuroscience at the CRUK/MRC Oxford Institute for Radiation Oncology has previously found that one element of the immune system, the inflammatory response, is important in the spread of breast cancer to the brain. Her team has previously found that certain inflammatory molecules are present at higher levels in brain metastases, and may be key drivers of tumour growth.
With funding from Breast Cancer Now, Professor Sibson and her team will undertake a three-year project to pinpoint which combinations of anti-inflammatory drugs, which are able to cross the BBB, reduce the growth of breast tumours in the brain most effectively, and whether these could also be given alongside radiotherapy with greater effect.
Professor Sibson said “We urgently need to find ways to treat brain metastases more effectively and improve survival rates. With this funding from Breast Cancer Now our aim is to increase treatment options for patients suffering metastatic spread to the brain. We hope that by targeting the innate immune system we can halt or reduce tumour growth, and enhance the effectiveness of radiotherapy.”
The scientists will first implant breast tumours into the brains of mice, before testing a range of anti-inflammatory drugs and examining the effect on tumour growth. The team will then combine the most effective anti-inflammatories with radiotherapy in mice to identify which combinations best control tumour growth in the brain. The researchers hope to identify new ways to predict which patients are most likely to benefit from anti-inflammatory drugs and radiotherapy. In addition, the team will explore how another component of the inflammatory response, adhesion molecules, are involved in tumour growth, and whether targeting these directly could also be an effective treatment strategy.
Dr Richard Berks, Senior Research Communications Officer at Breast Cancer Now said “Professor Sibson’s research could pave the way for new treatment combinations that could halt tumour growth in men and women whose breast cancers have sadly spread to the brain. Anti-inflammatory drugs are already used to treat arthritis – and if these new combinations are found to be effective, these drugs could be made available for treating patients with brain metastases much more quickly.
“It is essential that we find new ways to treat secondary breast cancer in the brain – to improve quality of life and chances of survival for those living with this debilitating disease.
“Our ambition is that by 2050, everyone who develops breast cancer will live. But if we are to achieve this, we desperately need to raise funds for research to find ways to stop the disease spreading. Professor Sibson’s project could help bring us one step closer to our 2050 vision and we’d like to thank our supporters across Oxford who continue to help make our world-class research possible.” 
Fiona Leslie, 49 from Aylesbury, is living with incurable metastatic breast cancer. Having first been diagnosed with breast cancer in 2013, Fiona underwent a mastectomy, radiotherapy and chemotherapy, before learning that her breast cancer had unfortunately spread to her lungs and her spine.
In April 2015, Fiona began receiving revolutionary drug Kadcyla, which kept her disease at bay for over two years, and enabled her to live a relatively normal life in the meantime. However in June 2017, scans showed that Fiona’s breast cancer had spread to her brain.
1. Local incidence and mortality survival statistics were provided on request by Public Health England, April 2017.

John Findlay wins Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) Prize

The CRUK Oxford Centre is delighted to announce that the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) recently awarded Centre member, John Findlay, its prestigious British Journal of Surgery prize for the best free paper presented at the 2017 AUGIS Scientific Meeting in Cork, Ireland. John is a Specialty Registrar in General Surgery in the Oxford Deanery, and a Senior Clinical Research Fellow in OesophagoGastric Surgery informatics at the NIHR Oxford Biomedical Research Centre.
The prize was awarded for his paper ’Staging gastric cancer with 18F-FDG PET-CT identifies frequent unsuspected metastases and patients of high risk of incurable disease, early recurrence and death’.
This study included 279 consecutive patients with stomach cancer (non-junctional gastric adenocarcinoma) who as part of their treatment at Oxford University Hospitals NHS Foundation Trust underwent a staging PET-CT scan. At present, there is little evidence that routinely using PET-CT in this context is useful. Consequently, it is not recommended by national and international guidelines. However, the Oxford OesophagoGastric Centre has routinely used cutting edge 18F-FDG PET-CT scanning technology for both oesophageal (gullet) and stomach cancer for more than 10 years. The test uses radio-labelled glucose molecules, which tend to concentrate in cancer tissues. These tissues then become visible, or ‘avid’, on the scan and may help provide information about the behaviour of cancer.
In the largest and most contemporary series to date, PET-CT was shown to detect incurable or metastatic cancer in approximately 7% of patients, despite their preceding CT scan being clear. Furthermore, the subgroup of patients who also had avid lymph nodes appeared to be at increased of such incurable disease, and also early cancer recurrence and death after surgery. This builds on previous findings from John’s research in oesophageal and gastro-oesophageal junctional cancer, and suggests PET-CT should also be considered routinely for patients with gastric cancer.
John is now exploring whether PET-CT should also be repeated before surgery if patients receive chemotherapy, and whether the response of avid nodes to this chemotherapy allows clinicians to monitor its effectiveness. He commented that he was honoured to receive this prize on behalf of his collaborators, and hopes that these findings will be able to improve staging and counselling for patients with stomach cancer, and also help identify patients who might benefit from additional investigations.

From bench to bedside in two years: collaborative science opens the way for a new drug for bowel cancer patients across the UK

Today a new drug will become available for patients with bowel cancer as part of a national clinical trial; based on a scientific discovery made only two years ago at the University of Oxford. A yeast genetics research group led by Professor Tim Humphrey in Oxford discovered an Achilles heel of certain cancer cells – mutations in a gene called SETD2. Prof Humphrey and his team showed that cancer cells with a mutated SETD2 gene were killed by an experimental drug being developed by Astra Zeneca called AZD1775 which inhibits a protein called WEE1. WEE1 was first discovered by British Nobel Prize winner Sir Paul Nurse.

The new research by the Humphrey group is exploiting the concept of ‘synthetic lethality’, in which a combination of two factors specifically kills cancer cells, and has the potential to be less toxic and more effective than existing treatments. Collaborating with Dr Andy Ryan’s group in Oxford, the two labs developed a test which would work in human cells to identify the presence or absence of SETD2. They found that about 1 in 10 bowel cancers and up to 50% of kidney cancers lose this marker and so have this susceptibility to being targeted with the drug. The mechanism of activity and the marker which identified the susceptible cells was published in Cancer Cell in November 2015.

The translational potential of this research was quickly developed by the CRUK/MRC Oxford Institute for Radiation Oncology, where clinical and basic scientists worked together with scientists at AstraZeneca to rapidly move the discovery towards a clinical trial. The existing national FOCUS4 trial for patients with bowel cancer provided an opportunity to get this exciting science tested clinically. Today the FOCUS4-C trial, which is open in 100 hospitals across the UK, and coordinated by the Medical Research Council (MRC) Clinical Trials Unit at University College London, will commence this new study.

For patients whose tumours lack a special histone marker, they will be eligible to enter a new part of the study testing the WEE1 inhibitor AZD1775. Patients who have bowel cancer which has spread to other organs and are inoperable can also be registered for the FOCUS4 trial during the initial 12 weeks of their first line treatment and have their tumour tested. The drug is not available except through ethically approved clinical trials.

Professor Tim Maughan, Chief Investigator of FOCUS4, from the CRUK/MRC Oxford Institute for Radiation Oncology, said: “We are very excited that we are able to test this very new approach to treatment for our bowel cancer patients. It is remarkable to be able to take a discovery in yeast cells through to opening a clinical trial on that evidence in less than 2 years. FOCUS4 was designed with this ability to move forward rapidly with new discoveries and test them in patients whose tumours express the characteristics which are predicted to make them sensitive to the new treatment. I am very hopeful this will bring benefit to our patients with bowel cancer.”

Professor Matt Seymour, one of the FOCUS4 clinical investigators and lead for cancer in the National Institute for Health Research Clinical Research Network, said: “What we are seeing here is seamless cooperation between highest-level university science, a major UK-based company, charity, the NHS and our world-leading government-supported clinical research infrastructure. This is UK medical science at its best and most efficient, and a great example of how our joined-up approach can drive exciting inventions rapidly though to clinical research with the potential to benefit NHS patients.”

Professor Tim Humphrey, Senior Group Leader in the CRUK/MRC Oxford Institute for Radiation Oncology, said: “We are excited to have discovered a new way to specifically kill bowel cancer cells with this mutation. To see our work in yeast potentially make a difference to patients in the clinic is very encouraging and shows the value of working together in a larger team of scientists within an Institute.”

Image showing kidney cancer cells before and after treatment with AZD1775, copyright CRUK/MRC Oxford Institute for Radiation Oncology

Dr Anderson Ryan, Senior Group Leader in the CRUK/MRC Oxford Institute for Radiation Oncology, said: “We’re now in the era of precision medicine and patients hope that new treatments will be targeted to their particular disease. This biomarker-driven trial aims to do just that – by using the molecular characteristics of tumours to decide which treatment to offer.”
Malcolm Pope, a former bowel cancer patient, commented: “As a patient, who was fortunate enough to be enrolled on a trial and given new treatment which worked for me, I feel that the progress being made in the Focus4 Trial regarding personalised cancer medicine is both exciting and greatly beneficial for today’s patients.”

Dr Áine McCarthy, Cancer Research UK’s senior science information officer, said: “Developing new targeted treatments for people with bowel cancer is essential to improve survival. Excitingly, these scientists have identified one such potential new treatment which will now be tested in a clinical trial to see if it can be used to treat bowel cancer. This work highlights the importance of carrying out clinical trials like FOCUS4 that can be adapted so that new drugs can be tested quickly, helping patients benefit from these drugs sooner.”