Personalisation: Genetic signatures for radiotherapy

Professor Catharine West, is one of only 35 scientists to have been awarded the prestigious Weiss medal and one of only 22 to be given the Bacq and Alexander award for radiation research, tells us how her decision to come to Manchester enabled her to pioneer developments in personalised radiotherapy.

Shortly after arriving in Manchester it became clear that this was the best place where I could do research which interested me. Radiotherapy is one of the most important treatments for cancer.

Importance of radiotherapy

Around 50% of cancer patients have radiotherapy and half of patients who are cured received radiotherapy as part of their treatment. Because of its importance in curing cancer, it’s vital to carry out research which increases our understanding of radiotherapy to optimise treatment for patients. There is a need for biomarkers that can help predict the effectiveness of different types of radiation and drug-radiation combinations, and whether patients are likely to suffer with long-term side effects.

My specific research focuses on trying to predict how cancer patients respond to radiotherapy and measuring hypoxia - a lack of oxygen - in patients. Hypoxia reduces the ability of radiotherapy to kill cancer cells, so I’m undertaking research to help increase our understanding of how hypoxia impacts on a patient’s outcome following radiotherapy and how it can be measured routinely.

Clinical campus

This research involves working extensively on samples taken from patients who are having or who have recently undergone radiotherapy for their cancer. The proximity to The Christie, which I soon found out was the largest radiotherapy centre in Europe, means that essentially no-one in the UK, or Europe, can compete with me in terms of recruiting large numbers of patient samples. I can run multiple, large scale projects precisely because of this access to large patient numbers.

Our clinical campus, with the co-localisation of the laboratory building on the hospital site, meant that I’ve always been based close to the clinical oncologists. This means that I have access to ask them any clinical questions that arise during any point in a study.  For every researcher seeking to achieve genuine patient-centric research, this multidisciplinary approach to research is essential. This existed here in Manchester from the outset, and its value in delivering high-quality patient relevant research cannot be underestimated.

Our unique geography, with the University just a stone’s throw away, has enabled me to conduct a number of internationally-leading radiobiology studies. This required working on samples from cancer patients, and being able to liaise with oncologists, pathologists and data experts to access information at different points of the research journey. I’ve been able to take a short walk along a corridor to talk to someone to discuss an idea, to sit with them face to face and discuss it before then taking another small walk to collect samples, take them to the lab and do more experiments.

Professor Catharine West

Catharine West is a Professor of Radiation Biology at The University of Manchester where she established the Translational Radiobiology Group.

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All the time I’m seeking and bringing in the expertise of colleagues from different disciplines in the University, such as physicists and statisticians. This culture of multidisciplinary working wasn’t like anything else I had seen before and, along with access to patients, provided another reason for me to stay.

The building of expertise, of knowledge and facilities that has been gained in Manchester through collaboration at every opportunity has resulted in us being able to expand radiotherapy related research several-fold in the time that I’ve been here. This unique Manchester offering of ours; the huge numbers of patients that we can treat and who can participate in our research, the ‘kit’ like the new proton research centre and the MR-linac machine, and the established culture of multidisciplinary working, means that we’ve attracted some of the best people in the world to come and contribute to our research expertise. What we can offer is incredible and everyone is noticing.

The amazing technological advances that followed the human genome project, which allowed rapid and affordable genome-wide analyses, to my mind offers the cancer research community some of the best opportunities for increasing our knowledge over the next decade.

International collaborations

Similarly, the associated opportunity of being able to carry out studies involving international collaborators where we run studies in parallel in multiple countries is definitely the way we need to go to speed up progress. If we can do this the opportunities for accessing more patients and increasing patient data means that we can find the patterns and upscale any learning. We’ve already made a significant contribution towards helping to respond to this need, globally.

We have led the creation of an international Radiogenomics Consortium to help facilitate collaboration and sharing of data for research, which is aimed at identifying the common genetic variants which affect the risk of toxicity following radiotherapy. We also currently lead an EU funded study that is carried out in eight countries that involves everyone collecting the same data.  Such a scaling up of data collection will massively increase our knowledge base.

It’s my hope that Manchester’s cancer research community become international leaders in biomarker-driven trials that personalise radiotherapy based on an individual patient’s biology. We’re already at the forefront of this and it’s my hope that in 15 or 20 years’ time, we’ll look back to how we used to treat everyone the same and regard it as archaic, precisely because each patient and their cancer is different. It would be fantastic to be the pioneers of achieving this shift.

We’ve already developed and validated a gene signature which characterises hypoxia status in head and neck cancer. Our research shows that cancer-specific gene signatures are needed to identify hypoxic tumours. These signatures can then be used as biomarkers in personalised healthcare approaches that will improve survival.

So far we have a phase III trial in head and neck cancer patients that is testing whether our signature can be used to select patients for treatment that targets hypoxia. The next step is to establish early phase biomarker driven trials in other cancers, and to increase collaborations with pharmaceutical companies.

All this is possible because of where we are and how we work together. Although I never intended to stay this long, I can honestly say that I’m very glad I did!