Improving the Efficacy of Immune-therapies for Melanoma Patients

In his recent commentary “Long-term survival with anti-PD-1-based immunotherapy, but what is the best approach?” in the Lancet Oncology Prof. Middleton, Cancer Research UK Oxford Centre Co-Director and Head of the Department of Oncology at the University of Oxford, discusses how the clinical community should look to build on the already transformative use of immune therapies to treat patients with melanoma.

Having more than doubled life expectancies for late-stage metastatic melanoma patients, there still remains significant potential for improving how and when these novel therapeutics are deployed, for which patients they are prescribed, and how to limit the side effects of these agents. These questions form the focus of efforts of cancer researchers across Oxford,  from  fundamental laboratory based research to national collaborations, and to clinical trials that are improving the lives of patients treated at the Oxford University Hospitals Foundation Trust and across the UK.


Marseille-Oxford Cancer Centres Collaboration (MOC3)


October 4th and 5th 2018 saw the first Marseille-Oxford Cancer Centres Collaboration  (MOC3) meeting, held in the beautiful location of Villa Gaby, Marseille. The meeting was held to initiate a new partnership between the Cancer Research UK Oxford Centre, the Cancer Research Centre of Marseille and the Institut Paoli-Calmettes.

The objectives of these cancer centres are closely aligned, across both basic and clinical activities. The aim of MOC3 is to benefit from the complementary state-of the-art expertise and experimental and clinical infrastructures of the two sites to tackle major clinical challenges faced by those treating cancer patients.

The first meeting focussed on genome stability and the DNA damage response, based upon the respective strengths in these fields of both centres, from basic through translational research and in clinical practice. Thirty-five Oxford scientists and sixty-five Marseille scientists including students, post-doctoral fellows and group leaders attended the meeting which consisted of talks, posters sessions and a workshop – the latter proving very successful in identifying new collaborative projects that will be up-and-running in the next few months.

A follow-up meeting will take place in 2019 in Oxford and will be aimed at identifying collaborative projects centred around the DNA damage response and the maintenance of genome stability in relationship to leukemias and pancreatic cancer.

Metabolic profiles of breast cancer linked to response to metformin treatment


(B)(extract): Static PET-CT images in coronal plane pre- and post-metformin are from an individual with an

increase in KFDG-2cpt following metformin;note increased uptake in axillary lymph nodes (circled).



An international collaborative team of medical oncologists, radiologists, cell biologists and bioinformaticians led from Oxford by Simon Lord and Adrian Harris, have identified different metabolic response to metformin in breast tumours that link to change in a transcriptomic proliferation signature.

Published last week in Cell Metabolism, the team integrated tumour metabolomic and transcriptomic signatures with dynamic FDG PET imaging to profile the bioactivity of metformin in primary breast cancer.

Simon Lord stated: “This study shows how the integrated study of dynamic response to a short window of treatment can inform our understanding of drug bioactivity including mechanism of action and resistance. Further work will look to identify how mutations in mitochondria may define the metabolic response of tumours.”

The group demonstrated that metformin reduces the levels of several mitochondrial metabolites, activates multiple mitochondrial metabolic pathways, and increases 18-FDG flux in tumours.

The paper “Integrated pharmacodynamic analysis identifies two metabolic adaption pathways to metformin in breast cancer” defines two distinct metabolic signatures after metformin treatment, linked to mitochondrial metabolism. These differential metabolic signatures apparent in tumour biopsy samples, did not link to changes in systemic metabolic blood markers including insulin and glucose, suggesting metformin has a predominant direct effect on tumour cells. Analysis of the dynamic FDG-PET-CT data showed that this novel imaging technique may have potential to identify early response to treatment that is not apparent using standard static clinical FDG-PET-CT.



Key point summary of the study:

  • There is great interest in repurposing metformin, a diabetes drug, as a cancer treatment
  • Two distinct metabolic responses to metformin seen in primary breast cancer
  • Increased 18-FDG flux, a surrogate marker of glucose uptake, observed in primary breast tumours following metformin treatment
  • Multiple pathways associated with mitochondrial metabolism activated at the transcriptomic level
  • Further evidence that metformin’s predominant effects in breast cancer are driven by direct interaction with tumour mitochondria rather than its effects on ‘host’ glucose/insulin metabolism


The study has been funded by Cancer Research UK, the Engineering and Physical Sciences Research Council, the Medical Research Council, and the Breast Cancer Research Foundation.


The published paper can be found at:


Content adapted from the original paper by Simon Lord et al.

AstraZeneca – Oxford Cancer Symposium (AZOCS), Thursday 13th September 2018 | Keble College, Oxford


AstraZeneca – Oxford Cancer Symposium (AZOCS)

Thursday 13th September 2018 | Keble College, Oxford


On Thursday 13th June, Keble College in Oxford hosted the
inaugural AstraZeneca – Oxford Cancer Symposium (AZOCS).


Over 125 researchers from Oxford and 90 cancer scientists from AstraZeneca and MedImmune attended to develop and establish a series of collaborative cancer research projects.


Almost 100 posters and 27 presentations showcased current
projects across all organisations, covering DNA Damage
, Early-Phase Clinical Trials, Enabling Technologies,
Epigenetics, Immuno-Oncology, and Radiation Oncology.



David Andrews from AstraZeneca in Cambridge commented:

“The feedback I have had from AstraZeneca and Medimmune colleagues has been overwhelmingly positive and it is clear there are many opportunities for us to collaborate – from target identification and validation all the way through to patient studies. We are very excited by the prospect of deploying our disease know-how, target knowledge and
portfolio of drugs in development alongside Oxford’s excellent
access to patients and patient-derived models.
Oxford’s specific disease and biological knowledge should also
enable us to more deeply understand biological targets

and bring benefit to patients.”


Chris Schofield from the Department of Chemistry in Oxford
emphasised: “The AZ-Oxford meeting showcased brilliant
science from both organisations aimed at enabling breakthrough treatments for cancer. The truly impressive research ranged from fundamental work on the origins of tumorigenesis to clinical studies. There is clearly enormous potential for industry and academic to work synergistically to cement the UK’s leading position in cancer research.”



Poster winners for the AZOCS Poster Prizes 2018 are:


A Fluorescent Reporter of Base Editing

Activity Reveals Editing Characteristics of APOBEC3A

– Matthew Coelho, AstraZeneca

A gene signature associated with PTEN activation defines good outcomes in intermediate-risk prostate cancer cases

– Chee Wee Ong, University of Oxford



If you attended the Symposium and would like to find out any more information about any of the presentations you saw, any of the posters, or further information on the CRUK Oxford Centre or AstraZeneca/MedImmune then please contact .


If you would like further information on how to download the Networking Meeting App ATTENDIFY, please contact .


AstraZeneca – Oxford collaborative Symposium September 2018 – Registration now closed

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.”

Identifying cancer’s food sensors may help to halt tumour growth

Oxford University researchers have identified a protein used by tumours to help them detect food supplies. Initial studies show that targeting the protein could restrict cancerous cells’ ability to grow.

A team from Oxford University’s Department of Physiology, Anatomy and Genetics led by CRUK Oxford Centre Member Dr Deborah Goberdhan worked with oncologist and researcher, Professor Adrian Harris, to understand the effects of this protein called PAT4.

Dr Goberdhan said: ‘We found that aggressive cancer cells manufacture more PAT4, which enables them to make better use of available nutrients than the cells around them – including healthy tissue.’

Cancer cells often have restricted access to the body’s nutrient-rich blood supply. The ability to sense and acquire nutrients is critical for a cancer to grow.

Dr Goberdhan’s and Prof Harris’s groups collaborated to develop an antibody that could be used to highlight PAT4 in human tissue samples. This was then used to study anonymous tumour samples taken from patients with colorectal cancer, a common form of the disease.

The results were compared to the known outcomes for the patients. Those who had higher levels of PAT4 in their tumours did less well than those with lower levels – being more likely to relapse and die.

The researchers then looked at what happened when PAT4 levels were reduced. They showed that by reducing PAT4 levels, cancerous tumours grew more slowly.

Dr Goberdhan said: ‘These findings support each other. Not only do higher levels of PAT4 mean a worse outcome, but lowering levels improves the situation. This means that we have identified a mechanism which cancer cells prefer to use and which we might be able to target as part of a combination treatment.’

The research, funded by Cancer Research UK, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council was published in the science journal Oncogene on 5 October 2015. It continues and may eventually provide a way of increasing survival from cancer.

Oxford University Hospitals becomes a Foundation Trust

Monitor, the regulator of NHS Services in England, has granted NHS Foundation Trust status to Oxford University Hospitals. At a Board meeting on 30 September 2015, Monitor agreed that Oxford University Hospitals NHS Foundation Trust should exist from today, 1 October 2015.

This decision comes after the Care Quality Commission gave OUH an overall rating of ‘Good’ in May 2014, and after scrutiny of the Trust’s quality, finances, service delivery and governance arrangements by the NHS Trust Development Authority and Monitor.

Sir Jonathan Michael, Chief Executive of Oxford University Hospitals NHS Foundation Trust said: “The work we have done to become a foundation trust has involved a journey of improvement that needed to happen anyway. Foundation trust status has been a stimulus to us to pursue this improvement but was not a destination in itself.

“Becoming a Foundation Trust is recognition of the work we have done to improve the quality and efficiency of our services for patients and the capability we have to continue these improvements. It also provides more local accountability through our membership and Council of Governors.

“I want to take this opportunity to thank our fantastic staff for their continued commitment to delivering high quality healthcare for all our patients. We recognise that becoming a foundation trust does not in itself solve the challenges facing us or the NHS nationwide. We will continue to focus on sustaining delivering safe and high quality care, living within our means and meeting national standards in a very difficult financial climate.”

Dame Fiona Caldicott, Chairman of Oxford University Hospitals NHS Foundation Trust said:

“Being a Foundation Trust will enable us to continue to improve our services by increasing the involvement of patients, staff and the local communities that we serve through our membership. It means that our Council of Governors will now play an important role in holding the Board of Directors to account, appointing Non-executive Directors and contributing to the strategic direction of the Trust.

“This is a most exciting event for the Trust and a vote of confidence in the achievements and capability of our staff.”

For more information on Oxford University Hospitals NHS Foundation Trust visit the website here.



Oxford to Pioneer Precision Cancer Medicine as a New Cancer Research UK Major Centre

The Cancer Research UK Oxford Centre was formed five years ago with the vision to harness the breadth and depth of research activity across the University and NHS Trust. There is now a rich and vibrant cancer research community that crosses traditional departmental and thematic boundaries. In recognition of the world-leading science taking place in Oxford, the innovative collaborations by Centre members, and the power of the cancer research network here, the Cancer Research UK Oxford Centre has been awarded Major Centre status by Cancer Research UK.

The Cancer Research UK Oxford Centre is one of the first to gain Major Centre status, receiving an extra £5 million in funding over the next two years. The Centre will continue to act as a vital research hub for the Cancer Research UK centre network, drawing together expertise, encouraging collaborative research, and bridging the gap between innovative laboratory work and benefits for patients.

The Major Centre strategy will focus on translating Oxford’s world-leading science across a broad range of disciplines, and ensure its translation into the clinic. Benefits for patients will be at the heart of its activities, drawing together expertise from different fields, including those not traditionally involved in cancer research. The Centre is ideally placed to deliver improved patient outcomes, and is driven by a bold and globally unique vision for how this will be achieved.

Priorities include the development of new immunotherapies and bringing together biologists, physicists, mathematicians and engineers to deliver new treatments. Investment will tie together advances in diagnostics, genomics, surgery, imaging, radiotherapy, and drug development to fulfil the Centre’s vision for precision medicine.

Professor Gillies McKenna, Director of the Cancer Research UK Oxford Centre, said: “We look forward to making the most of our role as a Major Centre and leader in cancer research in the UK. The new initiative will bring researchers and clinicians together in sustainable networks with longer term investment. This will allow us to combine the latest developments in radiotherapy and surgery with clinical trials of new drugs, providing the best evidence to guide cancer treatment and enhance cancer cure rates.”

Dr Iain Foulkes, Executive Director for Research Funding at Cancer Research UK, said: “The development of these Major Centres will accelerate national and international collaborations and improve treatments for patients. In each location we are developing cutting-edge approaches in how we treat the disease, be that the detection of individual tumour cells in the blood that allow us to monitor the disease or precision radiotherapy. With these Centres the UK goes from strength to strength in supporting the best cancer research in the world.”

The Cancer Research UK Manchester Centre, and Cancer Research UK Cambridge Centre have also achieved Major Centre status. The Cancer Research UK Manchester Centre will transform cancer treatments by developing new techniques in personalised medicine. They will profile blood samples at diagnosis and throughout the patient’s journey looking for DNA and cancer cells that are released from the tumour. The information will then be used not only to pick the right drug for the right patient but also help personalise surgery and radiotherapy. The Cancer Research UK Cambridge Centre will bring together the diverse strengths of Cambridge to create novel practical applications that will improve the detection and treatment of cancer. They will develop programmes in early detection, and integrative cancer medicine with the aim of developing new therapeutic approaches.