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.

Cancer Research UK boost for promising doctor

One of the UK’s most promising cancer doctors has received a prestigious award from Cancer Research UK to fund crucial research to develop and test urgently-needed treatments which use the body’s natural defences to target cancer.

The Cancer Research UK clinical trial fellowship award provides funding for up to two years and will enable Dr Victoria Woodcock to train at the Oxford Clinical Trials Research Unit at the Churchill Hospital site.

Dr Woodcock will gain skills and experience to design and lead clinical trials of the newest and most promising cancer medicines – to save more lives from the disease in the future.

Clinical trials are a vital part of cancer research. They are the best way to find out if a new treatment or procedure is safe, is better than the standard treatment or helps reduce side effects for patients.

Dr Woodcock’s work will focus on immunotherapy drugs – which use the body’s natural defences to attack cancer cells. These treatments hold great promise by looking for ways to teach the immune system to ‘remember’ the cancer and stop it coming back.

Dr Victoria Woodcock, Cancer Research UK clinical trial fellow, said: “As a cancer researcher it’s exciting to help develop drugs which I hope could one day save thousands of lives – it’s a great feeling. With this support and training in a clinical trials unit I’ll be able to design crucially important studies that will test new, more effective ways to treat cancer.”

Dr Ian Walker, Cancer Research UK’s director of clinical research, said: “In order to develop future cancer treatments we must invest in scientists and doctors – which is why we’re supporting talented doctors like Victoria through this programme.

“We fund more than 250 clinical trials across the UK, which cover a wide range of treatments including radiotherapy, immunotherapy, surgery and chemotherapy – with more than 27,000 patients taking part in one of our trials last year.

“We believe research like this to design and run new clinical trials of promising treatments will accelerate progress and increase survival from cancer.”