New clinical trial to tackle hard-to-treat leukaemia

A new clinical trial at Oxford’s Churchill Hospital plans to study the safety of a new experimental drug to treat a form of leukaemia, called Acute Myeloid Leukaemia (AML).

Acute myeloid leukaemia is the most common aggressive blood cancer and there are about 2,200 new cases in the UK each year. It can be hard to treat, especially in patients over 65 years of age and is often fatal within a year of diagnosis. Therefore, there is an urgent need for more effective therapies. The lack of suitable treatment has been identified as a major unmet need by the national blood cancer charity Bloodwise, which is co-funding the study.

The drug is in the earliest phase of clinical testing and does not have marketing authorisation or approval. The purpose of the clinical trial is to start to gain an understanding of the side effects of the drug and possibly identify early evidence of effectiveness in treating AML. Patients with AML and who are aged 18 and older are being sought for the study.

The drug is to be tested as part of a long term collaborative research project between cancer researchers at Oxford University in the United Kingdom and Stanford University in the United States. The clinical study is also a collaboration between Oxford University Hospitals NHS Foundation Trust, which runs the Churchill, the University of Oxford and Stanford University.

Research between the University of Oxford and Stanford University found that leukaemic stem cells that propagate the disease protect themselves from being “eaten” by immune cells by expressing a “don’t eat me” signal, called CD47.

Researchers developed this new drug to block CD47, and it is hoped will enable the body’s own immune cells to eliminate Acute Myeloid Leukaemia cells.

This clinical research is funded in the UK by the NIHR Oxford Biomedical Research Centre, the Medical Research Council and Bloodwise and in the US by the California Institute for Regenerative Medicine and Ludwig Cancer Research.

Chief Investigator for the clinical trial, Cancer Research UK Oxford Centre member and Professor of Haematology Paresh Vyas said: “This is an important study as it aims to provide much needed treatment for a large patient group where we have made limited impact in improving survival with good quality of life.

“It is also important as it is a radical new approach. It is an exciting and unique collaboration between two of the world’s most pre-eminent universities and is a great example of how universities and the NHS can develop drugs from concept to the clinic in partnership.”

George Freeman MP, Parliamentary Under Secretary of State for Life Sciences at the UK Government’s Department for Business, Innovation and Skills and the Department of Health, said: “This new drug could revolutionise our approach to tackling this form of leukaemia and potentially deliver a life-enhancing treatment so desperately needed by patients.

“Supporting the development of innovative medicines like this with trials in the NHS is why the Government invests £1 billion each year in the National Institute for Health Research, helping to confirm the UK’s position as a world-leader in medical research and accelerate access for NHS patients to new treatments.”

Dr Matt Kaiser, Head of Research at Bloodwise, said: “Drugs that harness the immune system have had considerable success in treating other types of blood cancer. This new type of treatment could be a very exciting prospect for patients with acute myeloid leukaemia, for whom alternatives to current treatments are desperately needed.”

Oxford ECMC announces new lead & CXD101 trial update

The Cancer Research UK Oxford Centre is delighted to announce that Dr Sarah Blagden is now the Experimental Cancer Medicine Centre (ECMC) lead for Oxford.

She brings a wealth of experience to her role as Oxford ECMC lead; following training in Cambridge and the Royal Marsden she went on to become Director of Imperial’s Early Cancer Trials Unit before joining Oxford in the Department of Oncology in 2015. Sarah has an outstanding international reputation and brings with her to Oxford ECMC many specialist skills as a clinician scientist. It is this experience in both academic and commercial early phase trials, alongside her leadership and vision, that will ensure the world-leading translational work in cancer here in Oxford continues to thrive.

The Oxford ECMC has been a key partner in the recent CXD101 trial. Celleron Therapeutics, the UK-based company developing personalised medicine for cancer patients, has today announced that significant clinical activity was observed in the first human trial of its pioneering personalised cancer treatment CXD101 in patients at Oxford’s Churchill Hospital with advanced treatment-resistant aggressive disease. The results also indicate that CXD101 has favourable safety and tolerability.

‘These results provide early clinical evidence that CXD101 is active against late stage cancer’ commented Professor Nick La Thangue, Founder and Chief Scientist, Celleron Therapeutics and Professor of Cancer Biology in the Department of Oncology at Oxford University. ‘CXD101 represents a new class of drugs with dual mode of action that not only targets tumour cells but also stimulates the patient’s immune system to fight the cancer. These are extremely encouraging and important results and we look forward to driving the clinical trials forward as fast as possible in aggressive cancers using our personalised treatment approach’.

A major challenge in drug development is that all cancer patients respond differently to treatment. Clinical trials with Celleron’s CXD101 drug are not only investigating the properties of the new drug but will also study a novel biomarker test, known as a companion diagnostic, to predict which patients can be successfully treated with the drug. This approach avoids the problem of treating patients who have little chance of benefiting from the treatment.

Dr John Whittaker, Celleron’s Chief Operating Officer commented ‘I am delighted to see Celleron, the Oxford Experimental Cancer Medicine Centre (ECMC) and Oxford Hospitals NHS Foundation Trust making excellent progress on Celleron’s proprietary targeted therapeutic, CXD101, which opens up new and exciting opportunities for treating aggressive types of cancer’.

Dr Graham Collins, Haematology Consultant at the Churchill Hospital, Oxford, remarked ‘ These are very promising results with a very well tolerated drug demonstrating clinical activity in aggressive lymphomas ‘.

Professor Mark Middleton, Chief Investigator for the trial and Deputy Director of the Cancer Research UK Oxford Centre noted ‘Whilst there’s a lot more work to be done, seeing patients benefit from CXD101 encourages us to study this exciting drug further. The support of the Experimental Cancer Medicine Centre has been key to developing and delivering the trial. It provides a way to bring new drugs to our patients, which might otherwise not happen’.

CXD101 is a next generation epigenetic immune-regulator representing a class of drug that kills cancer cells by blocking certain vital functions involved in gene expression, and reactivates the patient’s immune system so that cancer cells can no longer evade immune recognition. The trial is a unique partnership between Celleron Therapeutics, Oxford University Hospitals NHS Foundation Trust and the Oxford Experimental Cancer Medicine Centre. 

 

Queen’s Anniversary Prize for Oxford’s innovation in biomedical engineering

Awarded every two years, the Queen’s Anniversary Prizes recognise universities and colleges which have demonstrated excellence, innovation, impact and societal benefit.

Oxford’s Institute of Biomedical Engineering (IBME), which is a research institute in the Department of Engineering Science, has been at the forefront of innovation in medical technology for the past seven years, hosting world-leading projects such as the first human liver to be kept alive at body temperature outside the body.

Research carried out at the IBME has led to the establishment of nine commercial spinout companies, including OxSonics (ultrasound therapy), Oxehealth (cameras as health monitors), Intelligent Ultrasound (quality assurance of imaging services), and CN BioInnovation (fast-tracking of new drugs).

Professor Lionel Tarassenko CBE FREng FMedSci, Head of the Department of Engineering Science and Director of the IBME when it opened in 2008, said: ‘The move of engineering faculty to the IBME on the medical campus in Headington in April 2008 has been the catalyst for a remarkable period of innovation in medical technology in Oxford.

‘Oxford is leading the world in showing how engineers can work together with clinicians to address unmet needs in the prevention, diagnosis and treatment of major diseases and conditions.’

Professor Alison Noble OBE FREng, the current Director of the IBME and Cancer Research UK Oxford Centre member, added: ‘Since the opening of its building, IBME has more than doubled in staff, having raised over £50 million in research funding. The 16 academic staff and the 200 researchers working with them have completed more than 20 clinical trials, from pregnancy screening and diabetes self-management to organ preservation, and have spun out a new medical technology company each year.

‘We also have some exciting new initiatives under way that are underpinned by international collaborations, for example a Regenerative Medicine Technology Centre with China, and the Oxford Biodesign programme in collaboration with Stanford University.’

In this 11th round of the Queen’s Anniversary Prizes, 21 UK universities and colleges have been awarded Prizes recognising a wide range of innovative work across a host of disciplines. The Prize medals will be awarded at a special ceremony at Buckingham Palace in February.

Jo Johnson, Minister for Universities and Science, said: “The UK is a world leader in science and research, and the Queen’s Anniversary Prizes celebrate the achievements of our universities and colleges. The outstanding academics recognised with these awards bring benefits to the everyday lives of millions of people in the UK and deserve this high honour for their work.

Kieran Poynter, Chair of The Royal Anniversary Trust, said: “The Prizes in this biennial round again illustrate the variety and quality of innovative work being done in our universities and colleges. They encourage our institutions to think about what they are doing in terms of practical benefit as well as intrinsic quality. The work being recognised combines a track record of outstanding achievement with the promise of future development.”

More than 100 new companies – more than any other UK university – have been spun out from Oxford research in the past 25 years via the University’s technology transfer arm, Isis Innovation, with over 500 licences and consultancy agreements being signed in the last financial year alone.

Find out more about the Institute of Biomedical Engineering, here.

Conferring of the Roche Discovery Oncology Award

Roche has awarded four Early Stage Researchers the Roche Discovery Oncology Award at its Innovation Center in Penzberg near Munich. This year, the invitation is focused on the role of the extracellular matrix in the development of cancer. “The presentations of the young researchers were outstandingly prepared. Above all, the marked interdisciplinary combination of applied cancer research with technology and pre-clinical translational models was impressive,” said Christian Rommel, Global Head of Oncology Discovery, Roche Pharma Research & Early Development (pRED). He went on to say “Here, a vigorous generation of young scientists is blossoming!”

Maria Antsiferova of the ETH Zurich was awarded the first prize for her study of the growth factor, activin. Activin promotes healing where the skin is damaged. It can also facilitate the formation of skin tumours, however, by reprogramming various immune cells so that these are no longer optimally able to attack a tumour. Hence, the inhibition of activin may be a promising strategy for the prevention and treatment of skin cancer.

The second prize was awarded to Arseniy Yuzhalin for his work at the University of Oxford. He has developed a new technology for the investigation of the extracellular matrix. Using his research approach, the entirety of all extracellular matrix proteins, in which the tumour cells are embedded, can be studied. By this means, new target structures for the development of oncological agents could be found. Arseniy commented that “this Roche Oncology Award provides an excellent opportunity for young researchers, especially graduate students, to present their work to a wide audience. My work was highly appreciated by an international panel of juries, and I was awarded a prize in a very competitive environment. I believe this award is immensely valuable for my early career development and it also motivates me to carry on the fascinating research we do here at the Oxford Centre”

In order to do justice to the high standard of the papers presented, the jury awarded the third prize to two candidates. Verena Leidgens from the University of Regensburg impressed the jury with her translational research paper on the development of glioblastoma, an extremely aggressive cerebral tumour. She identified a particular tumour cell type, which migrates into the brain and, here, initiates tumour formation.

Albin Jeanne, University of Reims, developed a new approach enabling the inhibition of the development of blood vessels in tumours in the extracellular matrix. The jury acknowledged that he had discovered a new biological point of application in an essentially well-researched field of research such as anti-angiogenesis.

 

Image: Winners of the 3rd pRED Discovery Oncology Award 2015: Verena Leidgens, Albin Jeanne, Arseniy Yuzhalin and Maria Antsifevora with award presentor Christian Rommel (Roche pRED, Global Head of Oncology Discovery)
copyright Roche /Schebesta

 

Pancreatic Cancer UK funds new Oxford researcher in the fight against pancreatic cancer

National charity Pancreatic Cancer UK has today announced the award of £100,000 to a research team based at the University of Oxford. The grant will allow the addition of a new member to the team as part of the charity’s pioneering Future Leaders Fund, amounting to over £500,000 in similar grants across the UK. This award will support a student through a DPhil project which will be supervised by Dr Emmanouil Fokas and Professor Eric O’Neill.

In the project, the new researcher will investigate how the body’s own immune system, which normally fights infections, could be leading to treatment failures and poor survival rates in pancreatic cancer. The mixture of cells and proteins that surround pancreatic cancer cells, otherwise known as the tumour stroma, is particularly dense compared to other cancers and can make up to 90 per cent of the tumour mass. The stroma can become infiltrated with a specific type of immune cell which is thought to prevent chemotherapy from working properly.

This research aims to discover how and why this happens, with the hope that the findings will lead to treatments for the future that target the immune cells and therefore improve the effectiveness of chemotherapy.

Cancer Research UK Oxford Centre members Dr Emmanouil Fokas and Professor Eric O’Neill comment; “We are thrilled that Pancreatic Cancer UK’s Future Leaders Fund award has allowed us to bring in a bright young student to work alongside us on our investigations into the interactions between our immune system and pancreatic cancer. We are hoping that this research will help us to gain a better understanding of the reasons that so many tumours are resistant to chemotherapy and radiotherapy, in order for us to start developing strategies to improve the efficacy of current treatments.

Pancreatic Cancer UK’s Future Leaders Fund aims to attract new research talent and retain that expertise within the field, by supporting the research leaders of the future with both clinical and non-clinical research.

Today’s announcement coincides with Pancreatic Cancer Awareness Month. Throughout November, the charity is urging people to find out more about pancreatic cancer, which has the lowest survival rate of all the 21 common cancers, with just four per cent of people living for five years or more after diagnosis.

Pancreatic Cancer UK believes its ongoing support of pioneering, individual research grants will make a significant difference in a disease area where survival rates have remained the same for the last 40 years. Pancreatic cancer kills one person in the UK every hour and is the fifth most common cause of cancer deaths, yet receives only 1.4% of the total cancer research spend in the UK.

The Cancer Research UK Oxford Centre sees pancreatic cancer as a critical area of focus. Both Dr Emmanouil Fokas and Professor Eric O’Neill are members of the Cancer Research UK Oxford Centre Pancreatic Working Group, whose first meeting was held on World Pancreatic Cancer Day. This working group brings together 30 researchers and clinicians from multiple groups within the Oxford Centre network. The working group members come from a range of disciplines and by coming together they are able to further apply their world-leading science to areas of work that will have significant impact for patients.

Alex Ford, Chief Executive of Pancreatic Cancer UK, said: “As a charity that represents people with pancreatic cancer and their families, we have a responsibility to tackle the huge issue of under-funding into pancreatic cancer research as well as stimulating interest among the research community.

“We are delighted to be announcing this research at the University of Oxford as part of our latest round of grants under our Future Leaders Fund. We feel confident that the projects we have chosen to fund have the potential to make an important contribution to the fight against this disease. It is very exciting to be pairing up some of the most experienced researchers in the field and working together to begin to develop the leaders of the future in the fight against this terrible disease. We are looking forward to hearing of their findings as they work together with the aim of helping thousands of people with pancreatic cancer live for longer.”

To find out more about the Pancreatic Working Group at the Cancer Research UK Oxford Centre please contact cancercentre@oncology.ox.ac.uk

 

New treatment targets cancers with particular genetic signature

Oxford University researchers have found the Achilles heel of certain cancer cells – mutations in a gene called SETD2. Their findings will be presented to the National Cancer Research Institute conference in Liverpool today, Monday 2nd November.

It is well known that mutations drive cancer cell growth and resistance to treatment. However, these mutations can also become a weak point for a tumour. The Oxford team found that that was the case for cancer cells with mutations in a key cancer gene called SETD2.

Study author and Oxford Centre Member, Dr Timothy Humphrey said ‘Mutations in SETD2 are frequently found in kidney cancer and some childhood brain tumours, so we were excited when we discovered that a new drug we were studying specifically killed cancer cells with this mutation.’

The presentation will discuss how Dr Humphrey and his team showed that cancer cells with a mutated SETD2 gene were killed by a drug called AZD1775 that inhibits a protein called WEE1. WEE1 was first discovered by British Nobel Prize winner Sir Paul Nurse.

The team achieved this by exploiting the concept of ‘synthetic lethality’, where a combination of two factors kills a cancer cell. This has the potential to be a less toxic and more effective treatment than more standard approaches because it can specifically target cancer cells.

Co-author Dr Andy Ryan said: ‘When WEE1 was inhibited in cells with a SETD2 mutation, the levels of deoxynucleotides, the components that make DNA, dropped below the critical level needed for replication. Starved of these building blocks, the cells die. Importantly, normal cells in the body do not have SETD2 mutations, so these effects of WEE1 inhibition are potentially very selective to cancer cells.’

Importantly, the research team, funded by Cancer Research UK and the Medical Research Council, have also developed a biomarker test to identify SETD2 mutated tumours, something that can be used immediately in cancer diagnosis.

Professor Tim Maughan, Clinical Director of the Cancer Research UK/ Medical Research Council Oxford Institute for Radiation Oncology, said ‘This novel and exciting finding provides a new scientific basis for precision targeting of some cancers which are currently very difficult to treat, and we are now taking these findings into clinical trials.’

While there is still work to do before a treatment is available, the hope is that these findings will help to target other cancers with similar weak points and provide a step towards personalized cancer therapy.

Dr Humphrey will be available on the Cancer Research UK Oxford Centre booth at NCRI on Tuesday 3rd November at 10.20 to discuss his work with NCRI attendees. 

Oxford to lead work towards more personalised care for patients

Oxford is today named as a centre for excellence leading the drive to tailor more treatments to the needs of individual patients.

A Precision Medicine Catapult centre will be established in Oxford bringing together business and research to develop new products and services.

This project will be led by the Oxford Academic Health Science Network which will connect partners across the NHS, universities, research and industry with a particular focus on harnessing big data and developing new diagnostic tests. The aim is to accelerate the adoption of innovation in the NHS at pace and scale.

The announcement that Oxford will be one of six regional centres of excellence came from the Precision Medicine Catapult, funded by Innovate UK.

Precision medicine is the use of diagnostic tests and data-based insights to understand a patient’s disease more precisely leading to the selection of treatments which produce more predictable, safer and cost-effective outcomes.

Prof Gary Ford, Chief Executive of the Oxford Academic Health Science Network (AHSN), said: “Oxford has world- leading capability in precision medicine and a long history of developing new targeted therapies for patients.

“Designation as a Precision Medicine Catapult centre will speed up translation of scientific discovery into targeted treatments for patients and more rapid adoption into clinical services across our region and the wider NHS.”

Professor Keith Channon, Director of Research & Development at Oxford University Hospitals NHS Foundation Trust and Director of the National Institute for Health Research Oxford Biomedical Research Centre, said: “We are delighted that Oxford has been designated a Precision Medicine Catapult centre of excellence.

“This reflects the exciting innovations flowing from our NIHR Biomedical Research Centre and Academic Health Science Centre that will help us to develop and to introduce more personalised treatments for patients across the Oxford Academic Health Science Network region and beyond.”

Professor June Girvin, Pro Vice Chancellor and Dean of the Faculty of Health and Life Sciences at Oxford Brookes University, said: “Brookes is delighted to hear that Oxford will be a centre of excellence for precision medicine.

“As one of the four partners in the Oxford Academic Health Science Centre, we see this as another example of how health care research, education and practice in Oxford is absolutely at the forefront of innovation.”

Watch the below Oxford AHSN video, featuring Prof Sir John Bell, setting out the challenges and opportunities for Oxford in the field of precision medicine

 

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 Leads Recruitment of Cancer Patients for 100,000 Genomes Project

A project to unravel the genetic changes underlying rare disease and cancers of more than 1,200 patients and their families who are looked after by Oxford University Hospitals NHS Trust (OUHT) has started. The project will aid research, improve diagnosis and ultimately clinical outcomes so NHS patients can receive care based on cutting edge scientific techniques.

Eligible patients with rare diseases and cancers are being invited to provide health data and blood and tissue samples for whole genome sequencing – where a complete set of a person’s genes is decoded – for the national 100,000 Genomes Project, which was supported by a pilot by the Oxford Molecular Diagnostics Centre at the Trust’s John Radcliffe Hospital.

The Oxford cancer programme is the first in England to initiate recruitment this month and will collect approximately 1,200 samples from 600 cancer patients. Patients will be referred into the programme by the doctor looking after them. The programme is voluntary and patients will be considered only after they have given written consent. Samples will also be taken for other types of analyses for further research and extensive clinical outcome data will be collected. All samples will be sequenced by Illumina, the 100,000 Genomes Project’s sequencing partner.

Oxford NHS Genomic Medicine Centre clinicians will have access to results for validation and clinical action. The information captured will also be available to researchers for ethically approved research, to help develop new knowledge and treatments. By providing information about each disease’s unique genetic code, it is hoped that patients will benefit from treatment tailored to their needs while researchers will be able to study data from thousands of patients to develop new treatments.

The University of Oxford’s Wellcome Trust Centre for Human Genetics pioneered this new approach to genetic analysis with its WGS 500 Programme to sequence the complete genome of 500 patients in collaboration with Illumina. The success of WGS 500 helped to secure funding from the Cancer Research UK Oxford Centre, the National Institute for Health Research (NIHR) and The Wellcome Trust’s Health Innovation Challenge Fund, and the NIHR Oxford Biomedical Research Centre. This allowed the Oxford Molecular Diagnostics Centre to develop whole genome sequencing protocols and procedures for use in routine NHS clinical diagnostics and to evaluate the technique’s clinical effectiveness and cost implications for the NHS.

In the coming months, the Oxford NHS Genomic Medicine Centre will extend recruitment to its partner trusts in the region: Buckinghamshire Healthcare NHS Trust, Great Western Hospitals NHS Trust, The Royal Berkshire NHS Foundation Trust, Frimley Park Hospital NHS Foundation Trust and Milton Keynes Hospital NHS Foundation Trust. The entire three-year project will collect about 4,000 samples from about 1,600 patients.

Director of the Oxford NHS Genomic Medicine Centre and CRUK Oxford Centre Member Dr Anna Schuh said: “Oxford University Hospital NHS Trust’s designation as a Genomic Medicine Centre will allow eligible patients with rare diseases and their families and patients suffering from cancers to gain equitable access to state-of-the-art genomic diagnostics.

“For some of these patients, this new diagnostic approach will alter clinical management and can guide clinicians towards more effective treatment options. At the same time, by helping to recruit thousands of patients to this unique programme across England, we will make a significant contribution to collaborative research aimed at improving our understanding of these diseases which will ultimately lead to successful design of new therapies.”

Trust Director of Research & Development and NIHR Oxford Biomedical Research Centre Director Prof Keith Channon said: “We are extremely proud to be the first of the 11 Genomic Medicine Centres in England to offer this opportunity for patients with cancer. Oxford’s designation as a Genomic Medicine Centre, with the support of the NIHR Oxford Biomedical Research Centre reflects the highly productive collaboration between the OUHT and the University of Oxford’s world-class research departments in bringing benefits to NHS patients.”

Meet Sarah Blagden, Associate Professor of Experimental Cancer Therapeutics

The latest edition of OxfordMedSci news features an interview with Professor Sarah Blagden, Associate Professor of Experimental Cancer Therapeutics in the Department of Oncology and CRUK Oxford Centre Member, about her research investigating post-transcriptional mechanisms that drive cancer behaviour and researching novel cancer therapeutics. Prof Blagden is keen to hear from any researchers in the community interested in collaborating on potential cancer treatments. Find out more about her work below:

 

What are you doing now?

At the moment, I’m writing a study protocol for a small biotech company. They have discovered a drug that is effective against cancer (in the lab) but has not yet been tried in patients. My job is to translate the scientific data they have generated into a clinical trial. It is like writing a complicated recipe or putting together a jigsaw puzzle. The instructions on how to administer the drug need to be clear and safety is the priority. Once I’ve finished this draft, I will send it to the Early Phase Trials Unit in the oncology team at the Churchill Hospital so they can modify it and turn it into a clinical protocol that is ready to be reviewed by an ethics committee.

What are the challenges of early phase trials?

It helps that I have a science background because it drives me to question the mechanism behind any purported “wonder drug”. I don’t want to expose patients to anything that doesn’t make scientific sense. The patients entering these (Phase I) studies have exhausted all standard treatments available on the NHS and are coming to us with maybe only a few more months to live. It is vital that we don’t waste their time or introduce them to unpleasant side effects.

How did you get here?

I decided to become an oncologist when I was at medical school. Of all the medical specialities, I found oncology to be the most interesting. You have to be able to establish a rapport with your patients, but at the same time keep up with rapidly evolving science. When I became an oncologist, the cure for cancer was predicted to be only 10 years away. We know now that this was an optimistic estimation but new discoveries are published on an almost weekly basis and we have to adapt our practice in response to them. I was set to become a full time clinician until I spent 3 years in a fruit fly lab in Cambridge. The science was incredibly complex and frustrating but I had a few break-through moments. One you have had a “science high” you become addicted! After that, I wanted to bring research more closely into my day-to-day oncology practice and, hence, started working as a clinician scientist. I worked at Imperial College for 9 years and, in April 2015, moved to Oxford.

What topics are you pursuing in your lab? What are the challenges?

In my lab we look at messenger RNA (mRNA) translation and cancer. Since the human genome was sequenced on 2001, there has been an assumption that cancer behaviour is predominantly dictated by inherited or acquired genetic mutations. In our lab, we have a different focus, not on the genes themselves but how they generate proteins. In cancer, the “middle man”, mRNA, is an unreliable messenger and can create much more or less protein than the gene has transcribed. In some situations, these alterations to protein content are enough to turn a cell cancerous and make existing cancers more aggressive and treatment-resistant. The purpose of my lab is to dissect these mechanisms and identify which of them could be targeted with drugs. The challenge of this type of research is the techniques that we use to identify RNA and its protein complexes are new and constantly changing. Also, it has taken a while for the cancer research community to appreciate the importance of mRNA dysregulation in cancer, but thankfully this has changed in recent years.

How has being at Oxford helped the work of your lab?

Oxford is a hot bed of RNA enthusiasts, so it feels like a homecoming for me. There are the likes of Nick Proudfoot the RNA polyadenylation expert, Chris Norbury and Colin Goding, to name just three. There is a very collaborative feel here, so I have no doubt this is the perfect fit for my group.

Are there any collaborations/partnerships you’d like to pursue with colleagues in Oxford?

I’m really interested in talking to labs with research that might eventually lead to a cancer treatment. Scientists can be daunted by the thought of taking something from the lab into the clinic, the so-called “bench to bedside” transition. It is actually simpler than it seems and I can help develop their ideas into a clinical trial outline that can be included in grant proposals or business plans. It is interesting for me to be involved in new areas of research and have the tantalising thought that they might be the next “big thing” for cancer. I’m also keen to involve scientists in upcoming clinical studies. Quite often, pharmacological companies hit upon a cancer drug without fully understanding the science behind it. Scientists here may have devoted their entire profession to one particular cancer signalling pathway and can advise the companies on what biomarkers can be used or, better still, offer collaborations with them to explore aspects of the biology in more detail. I see this matchmaking role as a very important part of my job.

What are the bigger questions in your field? How do you see your field developing in the next ten years? What are the obstacles (technical or otherwise) to getting there?

From a clinical perspective, a big question is how we are going to be able to get the best drugs to cancer patients in the future. With the financial constraints on the NHS, we need to think of creative solutions. One is to bring clinical trials into the mainstream, as a part of the routine care for all patients. At the moment, about 12% UK patients enter a clinical trial during their cancer journey. By increasing the number of studies available nationally, patients will have access to ground breaking treatments at a minimal cost to the NHS. But this requires a national overhaul of how studies are conducted,particularly their cost and speed. Because Oxford prioritises clinical drug development, these ideas are already embedded into their practice. The Early Phase Trials Unit is impressively efficient and gives cancer patients a choice of studies to participate in.

From the research point of view, I would like to see mRNA translation inhibitors enter cancer trials in the UK. There is a network of RNA biologists in Oxford, Leicester, Manchester and beyond who share this view and have identified new drug targets. It would be immensely satisfying to conduct some of these studies in Oxford and put my beliefs to the test. I have also been lucky enough to work with biotech companies and labs that have developed effective anti-cancer drugs. It is exciting to watch patients’ lives being transformed with a drug that has yet to hit the mainstream. Hence I am here, writing this protocol, and sincerely hoping it will be the next cancer breakthrough.

 

You can follow Sarah on Twitter, and find out more about her work on the Department of Oncology website.

The interview originally appeared in Issue 24 of OxfordMedSci News.