Understanding early evolution of hard to treat cancer

Dr Phil Jones, a clinician scientist based at the Wellcome Trust Sanger Institute and University of Cambridge, is developing powerful model systems that will help transform our understanding of the earliest steps in the evolution of oesophageal cancer and test interventions to block its development.

Supporting a cancer of unmet need

Phil’s role as a medical oncologist gives him valuable insight to the current treatments for oesophageal cancer and the impact they have on patient’s quality of life. He is optimistic about the possible impact of his research, which looks at how single oncogenic alterations can develop into cancer.

“Globally oesophageal cancer is a significant killer, and currently the treatment is aggressive and comes with a major impact on quality of life. We have recently developed a new method that allows us to map mutations in human tissues, so we can extend our insights from model systems into humans and build a platform for translational studies. This will greatly accelerate progress in this area.”

So little is known about the ‘pre-cancer’ phase in epithelial cancer development that most of our experiments are yielding significant new insights.

Overcoming the challenges of working on a cancer of unmet need

In 2014, we set out an ambition to boost investment and develop capacity in four cancers recognised as having an unmet need, including oesophageal cancer. Phil believes the focus we have placed on this area is delivering significant value for the research community and patients.

Phil’s group are studying how normal cell behaviour is altered by mutations in the earliest stages of cancer development, before the formation of a visible tumour. His group has pioneered the use of large-scale genetic lineage tracing to quantify cell behaviour in vivo, he will use this in combination with genetic manipulation to further explore clonal evolution in oesophageal cancer.

“In 2015 CRUK organised a very helpful workshop bringing together UK and international researchers, which was very effective at kick-starting the new focus on oesophageal cancer in the UK and connecting researchers in different areas.”

The oesophageal community in the UK remains relatively small but Phil says this limitation has helped unite researchers with a shared goal.

“I have found that people are keen to engage and collaborate. The field currently lacks some of the necessary research tools that have facilitated progress in other tumour types. Our group and others are working hard to develop these to provide a scientific platform for younger researchers starting out in oesophageal cancer research.”

Collaboration at the heart of multidisciplinary research

Phil is leading the programme, but to help him build the necessary scientific tools to enable the study, he is working with a range of collaborators in computational biology, statistics and mathematics as well as experimental biologists. The combination of expertise he is drawing together is a key strength of his programme award.

Good collaborations are grown over time and enable both parties to do things together they could not do apart. Investing time in all these relationships has been transformative for our research.

Advice for future applicants: discuss your idea with the team at CRUK

Our Programme Awards are open to a wide range of disciplines and research areas, and support world-leading research to transform our understanding of cancer biology.. Phil recognised that to begin the application process he needed a focused research question with clearly defined outputs.

“By starting with a question that can provide a platform for future work, you are in a good position to discuss your idea with the team at CRUK.”

When it came to presenting his application to the committee he knew that he needed to consider the range of backgrounds and research expertise within the committee and plan for challenges he might get.

“A good abstract and lay summary will be a huge help in orientating panel members outside your area. I also made sure I prepared to discuss my risk management strategy and any contingency plans.”