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ESMO Translational Research Award: How Evolutionary Biology is Changing Approaches to Cancer Treatment

03 Sep 2019

Prof. Charles Swanton is the winner of this year’s ESMO Translational Research Award, which will be presented to him at the upcoming ESMO Congress 2019 in Barcelona. (1) The award recognises Swanton’s outstanding contributions to translational medicine, over the course of a career dedicated to understanding the biological underpinnings of treatment resistance in cancer and developing new methods to overcome it in the clinic. In an interview, the Royal Society Napier Professor of Cancer and Chief Clinician at Cancer Research UK (CRUK) explained what motivates him, how Charles Darwin put him on the right path, and why he is not quite ready to call his important work “successful”. 

What attracted you to translational medicine?

I was in the MD PhD programme of the University College of London in the mid-90s, so I completed my PhD while I was in medical school to qualify as a doctor: In a sense, I became a scientist before I became a doctor. Since then I have always wanted to combine a career in science with actual medical practice: I wanted to design and run clinical trials and understand why certain drugs were working and why others were not, to really get to the bottom of the problem of drug resistance and treatment failure. My work over the last 20 years has been focused primarily on trying to understand that problem.

You are now a Royal Society Napier Professor and Chief Clinician at Cancer Research UK. What exactly does your work entail?

In my role at CRUK, I am mainly responsible for the training and development of the next generation of clinical academics in the UK. As a Royal Society Napier Professor of Cancer, I am able to run my own lab, where we are currently studying tumour evolution in the course of the TRACERx study funded by Cancer Research UK, focusing on non-small cell lung cancer. We want to see if we can predict how a cancer will evolve and identify mechanisms of branched evolution and metastasis. We are also testing the use of circulating tumour DNA (ctDNA) in conjunction with these evolutionary methods we’re developing to identify signs of a tumour coming back after surgery, in advance of anything being visible on a CT scan. In addition, we are designing new clinical trials to target multiple clonal mutations through neoantigen-directed T-cell therapies, which are due to begin this year.

What do you consider to be your most important scientific finding?

Witnessing the speed at which tumours acquired drug resistance, it seemed logical that cancer drug resistance followed the principles of Darwinian evolution, but a decade ago there was little evidence to justify that proposal. Pioneering scientists including Heppner, Nowell and many others had drawn the same conclusions decades before. When I created my own research group in 2008, one of the key questions we set out to test was whether Darwinian evolution and natural selection provide a rational basis to understand treatment failure. One of the ways we did this was to sequence tumour DNA from multiple areas of a tumour to investigate how different or similar distinct regions of the same tumour were at the single nucleotide level. Almost every tumour we looked at showed evidence of branched evolution: the phenomenon of Darwinian selection was very clear and occurring again and again in solid tumours. Our work, and that of others, has now shown conclusively that this is a fundamental principle of tumour evolution and, in many cases, a likely underlying cause of treatment failure.

What excites you about your work?

Discovering new rules in nature really excites me, and I am passionate about doing this in a way that will have direct benefits for patients. I also love working in a big team that makes all of this possible: seeing it grow and junior scientists from the lab become successful and lead their own groups has been one of the most enriching aspects of my job in the last few years.

What is the message you would like to leave to your collaborators?

I know everybody says this, but it really is true for my lab: none of our progress would have been possible without teamwork and the valuable contributions of incredibly bright and motivated scientists and clinicians. The funding from Cancer Research UK and support from the Francis Crick Institute has also been essential to our work, which requires huge resources and collaboration on a national scale. Everyone who has been a part of this effort has been magnificent, and this prize is really for them, much more than for me – it’s a testament to their achievements.

How do you relate this award to your own success?

Our tumour evolution and neoantigen research is contributing to clinical trials of new treatment possibilities like T-cell therapies targeting clonal neoantigens. We are particularly excited about the role of circulating tumour DNA in the detection of minimal residual disease following surgery to allow treatment escalation in the adjuvant setting within new clinical trial designs.  In our field, however, success will ultimately be defined by research that markedly improves outcomes or quality of life for patients – that is really all that matters. To me, translational research is about taking basic scientific discoveries to the clinic and increasing patients’ survival and quality of life. I don’t think we have achieved that yet, and I won’t consider us successful until we do. Therefore, I see this award as an encouragement to continue our work over the next decade.       

What role has ESMO played in your career? 

ESMO is a key driver of translational research in cancer. The Society provides a hugely important network for collaboration between fellow oncologists and scientists, which has become the focal point of European oncology interactions on a yearly basis. It has played a big part in my life over the last several years and continues to do so. In my field, networking and collaboration are absolutely crucial. As we are subdividing study cohorts within individual tumour types, we are dealing with increasingly small numbers of patients: we need to collaborate at an international level to make clinical trials possible and biomarker studies feasible. This could not happen without big organisations like ESMO that help to bring the community together.

What do you think will be the next big thing in translational research?

Understanding tumour evolution and heterogeneity, the mechanisms behind it, how the immune system is subverted by an evolving cancer, and how to track that evolution in real time, couldn’t be more important. This is a crucial area of translational medicine, not just for the future of clinical trial design but also for developing optimal therapeutic approaches that could allow us to prevent cancer recurrence.

Who has inspired you in life?

Charles Darwin, with his phenomenal insights into evolution and the fundamental principles and underpinnings of natural selection. They are key to our understanding of cancer today, and the fact that he developed these principles with limited scientific tools is truly remarkable. He taught us that meticulous work and sustained effort in a single field can really change the world, and he has inspired our lab to think more deeply and continue our efforts in this specific area of research.

References

  1.  Prof. Charles Swanton will receive the ESMO Translational Research Award and will present a Keynote Lecture entitled: “Cancer through an evolutionary lens” during the ESMO 2019 Opening Ceremony,  Friday 27 September, 11:45-13:30, Barcelona Auditorium

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